NUVL soars on 44% ORR ROS1 data; FDA grants RTOR for July 2025 NDA

Q: What is the pivotal ORR achieved by Nuvalent's zidesamtinib in pre-treated ROS1-positive NSCLC?

44 % (51/117; 95 % CI 34-53) per blinded independent central review.

Q: When will Nuvalent (NUVL) begin its rolling NDA submission for zidesamtinib?

The company plans to initiate the rolling NDA in July 2025 and complete it in Q3 2025.

Q: How durable were responses to zidesamtinib in the pivotal dataset?

Kaplan-Meier analysis showed 84 % of responders remained in response 鈮�6 months and 78 % 鈮�12 months.

Q: What intracranial efficacy did zidesamtinib demonstrate?

In patients with measurable CNS disease (n = 56), the IC-ORR was 48 % with 20 % complete responses.

Q: What is the efficacy of zidesamtinib in TKI-na茂ve ROS1-positive NSCLC patients?

Preliminary data showed an 89 % ORR (31/35) and DOR 鈮�6 months in 96 % of responders.

Q: What other late-stage program did Nuvalent highlight in the 8-K filing?

The ALKAZAR Phase 3 trial evaluating neladalkib vs. alectinib in ALK-positive NSCLC, with enrollment expected early H2 2025.

[8-K] Nuvalent, Inc. Reports Material Event

Filing Impact

(Moderate)

Filing Sentiment

(Neutral)

Form Type

8-K

Rhea-AI Filing Summary

Nuvalent, Inc. (NASDAQ: NUVL) filed an 8-K disclosing pivotal Phase 1/2 data and regulatory progress for its lead ROS1-selective inhibitor, zidesamtinib, in ROS1-positive non-small cell lung cancer (NSCLC).

Pivotal dataset 鈥� TKI pre-treated setting (n = 117)

Objective response rate (ORR, RECIST 1.1, BICR): 44 % (51/117; 95 % CI 34-53).
Durability: Kaplan-Meier probability of remaining in response 鈮�6, 鈮�12 and 鈮�18 months was 84 %, 78 % and 62 %, respectively; emerging median DOR 22.0 months.
Activity across resistance profiles: ORR 54 % in patients with ROS1 G2032R mutation (n = 26) and 51 % in those with only one prior TKI (crizotinib or entrectinib; n = 55).
Intracranial efficacy (baseline measurable CNS disease, n = 56): IC-ORR 48 % with 20 % complete responses; IC-DOR 鈮� 12 months 71 %.
Safety (n = 432 at RP2D): most frequent TEAEs 鈮�15 % were peripheral edema (36 %), constipation (17 %), CPK increase (16 %), fatigue (16 %), dyspnea (15 %); dose reductions 10 %, discontinuations 2 %.

Preliminary TKI-na茂ve data (n = 35)

ORR 89 % (31/35); DOR 鈮�6 & 鈮�12 months 96 %.
Intracranial subset (n = 6): IC-ORR 83 % with 67 % CR; no CNS progression among responders.
Global enrollment for the TKI-na茂ve cohort has reached 104 patients.

Regulatory & pipeline milestones

Completed pre-NDA meeting; FDA agreed to accept zidesamtinib NDA into the AG真人官方-Time Oncology Review (RTOR) pilot.
Rolling NDA submission to begin July 2025, targeted completion Q3 2025; company is also discussing 鈥渓ine-agnostic鈥� expansion with FDA.
Front-line strategy advances: first preliminary data from TKI-na茂ve cohort reported; Phase 3 ALKAZAR trial of neladalkib vs. alectinib in ALK-positive NSCLC set to initiate enrollment early H2 2025.

Investor takeaways: The pivotal efficacy, durability and intracranial activity in a heavily pre-treated population, combined with an RTOR-enabled NDA timeline and a diversified front-line development plan, collectively strengthen Nuvalent鈥檚 near-term commercial prospects and strategic positioning in the competitive ROS1/ALK TKI landscape.

Nuvalent, Inc. (NASDAQ: NUVL) ha presentato un modulo 8-K divulgando dati cruciali di Fase 1/2 e progressi regolatori per il suo inibitore selettivo ROS1 di punta, zidesamtinib, nel carcinoma polmonare non a piccole cellule (NSCLC) positivo per ROS1.

Dataset chiave 鈥� pazienti precedentemente trattati con TKI (n = 117)

Tasso di risposta obiettiva (ORR, RECIST 1.1, BICR): 44% (51/117; intervallo di confidenza 95% 34-53).
Durata: la probabilit脿 Kaplan-Meier di mantenere la risposta per 鈮�6, 鈮�12 e 鈮�18 mesi 猫 stata rispettivamente dell鈥�84%, 78% e 62%; mediana emergente della durata della risposta (DOR) pari a 22,0 mesi.
Attivit脿 attraverso profili di resistenza: ORR del 54% nei pazienti con mutazione ROS1 G2032R (n = 26) e del 51% in quelli con un solo precedente TKI (crizotinib o entrectinib; n = 55).
Efficacia intracranica (malattia CNS misurabile alla baseline, n = 56): ORR intracranica (IC-ORR) del 48% con il 20% di risposte complete; durata della risposta intracranica (IC-DOR) 鈮� 12 mesi al 71%.
Sicurezza (n = 432 alla dose raccomandata per la fase 2): eventi avversi correlati al trattamento (TEAE) pi霉 frequenti 鈮�15% sono stati edema periferico (36%), stitichezza (17%), aumento della CPK (16%), affaticamento (16%), dispnea (15%); riduzioni di dose 10%, interruzioni 2%.

Dati preliminari in pazienti na茂ve a TKI (n = 35)

ORR 89% (31/35); durata della risposta 鈮�6 e 鈮�12 mesi al 96%.
Sottogruppo intracranico (n = 6): IC-ORR 83% con 67% di risposte complete; nessuna progressione CNS tra i responder.
L鈥檃rruolamento globale per la coorte na茂ve a TKI ha raggiunto 104 pazienti.

Traguardi regolatori e pipeline

Incontro pre-NDA completato; FDA ha accettato di includere la NDA di zidesamtinib nel programma AG真人官方-Time Oncology Review (RTOR).
Invio rolling della NDA previsto per luglio 2025, completamento stimato per il terzo trimestre 2025; la societ脿 sta inoltre discutendo con la FDA una possibile espansione 鈥渓ine-agnostic鈥�.
Progressi nella strategia di prima linea: primi dati preliminari dalla coorte na茂ve a TKI riportati; lo studio di Fase 3 ALKAZAR, che confronta neladalkib con alectinib nel NSCLC ALK-positivo, inizier脿 l鈥檃rruolamento nella prima met脿 del 2025.

Considerazioni per gli investitori: L鈥檈fficacia cruciale, la durata della risposta e l鈥檃ttivit脿 intracranica in una popolazione fortemente pretrattata, unite a una tempistica NDA abilitata da RTOR e a un piano di sviluppo diversificato in prima linea, rafforzano complessivamente le prospettive commerciali a breve termine di Nuvalent e il suo posizionamento strategico nel competitivo mercato dei TKI ROS1/ALK.

Nuvalent, Inc. (NASDAQ: NUVL) present贸 un formulario 8-K revelando datos clave de la Fase 1/2 y avances regulatorios para su inhibidor selectivo de ROS1 l铆der, zidesamtinib, en c谩ncer de pulm贸n no microc铆tico (NSCLC) positivo para ROS1.

Conjunto de datos crucial 鈥� pacientes previamente tratados con TKI (n = 117)

Tasa de respuesta objetiva (ORR, RECIST 1.1, BICR): 44% (51/117; intervalo de confianza del 95% 34-53).
Durabilidad: la probabilidad Kaplan-Meier de mantener la respuesta 鈮�6, 鈮�12 y 鈮�18 meses fue del 84%, 78% y 62%, respectivamente; mediana emergente de duraci贸n de la respuesta (DOR) de 22,0 meses.
Actividad en perfiles de resistencia: ORR del 54% en pacientes con mutaci贸n ROS1 G2032R (n = 26) y 51% en aquellos con un solo TKI previo (crizotinib o entrectinib; n = 55).
Eficacia intracraneal (enfermedad CNS medible en l铆nea base, n = 56): IC-ORR 48% con 20% de respuestas completas; IC-DOR 鈮� 12 meses 71%.
Seguridad (n = 432 en RP2D): los eventos adversos relacionados con el tratamiento (TEAE) m谩s frecuentes 鈮�15% fueron edema perif茅rico (36%), estre帽imiento (17%), aumento de CPK (16%), fatiga (16%), disnea (15%); reducciones de dosis 10%, interrupciones 2%.

Datos preliminares en pacientes na茂ve a TKI (n = 35)

ORR 89% (31/35); DOR 鈮�6 y 鈮�12 meses 96%.
Subgrupo intracraneal (n = 6): IC-ORR 83% con 67% de respuestas completas; sin progresi贸n CNS entre respondedores.
La inscripci贸n global para la cohorte na茂ve a TKI ha alcanzado 104 pacientes.

Hitos regulatorios y de pipeline

Reuni贸n pre-NDA completada; FDA acord贸 aceptar la NDA de zidesamtinib en el piloto AG真人官方-Time Oncology Review (RTOR).
La presentaci贸n rolling de la NDA comenzar谩 en julio de 2025, con finalizaci贸n prevista para el tercer trimestre de 2025; la compa帽铆a tambi茅n est谩 discutiendo una expansi贸n 鈥渓ine-agnostic鈥� con la FDA.
Avances en la estrategia de primera l铆nea: primeros datos preliminares del cohorte na茂ve a TKI reportados; el ensayo de Fase 3 ALKAZAR de neladalkib vs. alectinib en NSCLC ALK-positivo comenzar谩 el reclutamiento a principios del segundo semestre de 2025.

Conclusiones para inversores: La eficacia clave, durabilidad y actividad intracraneal en una poblaci贸n fuertemente pretratada, combinadas con un calendario NDA habilitado por RTOR y un plan de desarrollo diversificado en primera l铆nea, fortalecen colectivamente las perspectivas comerciales a corto plazo de Nuvalent y su posicionamiento estrat茅gico en el competitivo panorama de TKI ROS1/ALK.

Nuvalent, Inc. (NASDAQ: NUVL)電� ROS1 鞏戩劚牍勳唽靹疙彫韽愳晹(NSCLC)鞐愳劀靹犽弰鞝侅澑 ROS1 靹犿儩鞝� 鞏奠牅鞝滌澑歆€雿办偧韹半嫏鞚� 欷戨寑頃� 1/2靸� 雿办澊韯� 氚� 攴滌牅歆勴枆靸來櫓鞚� 瓿店皽頃橂姅 8-K毳� 鞝滌稖頄堨姷雼堧嫟.

頃奠嫭雿办澊韯� 靹疙姼鈥� TKI 旃橂 瓴巾棙鞛� (n = 117)

臧濌磤鞝� 氚橃潙毳�(ORR, RECIST 1.1, BICR): 44% (51/117; 95% 鞁犽甑皠 34-53).
歆€靻嶌劚: Kaplan-Meier 攵勳劃鞐愳劀 6臧滌洈, 12臧滌洈, 18臧滌洈鞚挫儊氚橃潙鞙犾 頇曤鞚€ 臧侁皝 84%, 78%, 62%鞓€鞙茧┌, 欷戧皠氚橃潙歆€靻� 旮瓣皠(DOR)鞚€ 22.0臧滌洈搿� 雮橅儉雮姷雼堧嫟.
雮挫劚頂勲頃勲硠頇滌劚霃�: ROS1 G2032R 霃岇棸氤€鞚� 頇橃瀽(n=26)鞐愳劀 ORR 54%, 鞚挫爠鞐� 頃� 氩堨潣 TKI 旃橂(韥Μ臁绊嫲雼� 霕愲姅鞐旐姼霠夗嫲雼�; n=55)毳� 氚涭潃頇橃瀽鞐愳劀 ORR 51%毳� 旮半頄堨姷雼堧嫟.
雵岆偞須姤(旮办爛靹犾棎靹� 旄§爼臧€電ロ暅欷戩稊鞁犼步瓿� 歆堩櫂, n=56): 雵岆偞 ORR 48%鞐� 20% 鞕勳爠氚橃潙; 12臧滌洈鞚挫儊雵岆偞氚橃潙歆€靻嶋(IC-DOR) 71%.
鞎堨爠靹� (RP2D 鞖╇焿, n=432): 15% 鞚挫儊氚滌儩頃� 欤检殧旃橂 甏€霠� 鞚挫儊氚橃潙(TEAE)鞚€ 毵愳磮攵€膦�(36%), 氤€牍�(17%), CPK 歃濌皜(16%), 頂茧(16%), 順疙潯瓿る瀫(15%)鞚措┌, 鞖╇焿臧愲焿鞚€ 10%, 欷戨嫧鞚€ 2%鞓€鞀惦媹雼�.

TKI 氙戈步項橃瀽鞓堧箘雿办澊韯� (n = 35)

ORR 89% (31/35); 6臧滌洈氚� 12臧滌洈鞚挫儊氚橃潙歆€靻嶋 96%.
雵岆偞頃橃渼攴鸽９ (n = 6): 雵岆偞 ORR 83%鞐� 67% 鞕勳爠氚橃潙; 氚橃潙鞛� 欷� 欷戩稊鞁犼步瓿� 歆勴枆鞐嗢潓.
TKI 氙戈步項橃瀽旖旐樃韸胳潣鞝� 靹戈硠霌彪 頇橃瀽靾橂姅 104氇呾棎霃勲嫭頄堨姷雼堧嫟.

攴滌牅氚� 韺岇澊頂勲澕鞚� 鞚挫爼響�

靷爠 NDA 氙疙寘鞕勲; FDA電� 歆€雿办偧韹半嫏 NDA毳� 鞁れ嫓臧� 膦呾枒頃� 瓴€韱�(RTOR) 韺岇澕霟� 頂勲攴鸽灗鞐� 靾橂澖頃橁赴搿� 霃欖潣頄堨姷雼堧嫟.
2025雲� 7鞗旊秬韯� 靾滌皑鞝� NDA 鞝滌稖鞁滌瀾鞓堨爼, 2025雲� 3攵勱赴鞕勲 氇╉憸; 須岇偓電� FDA鞕€ 鈥滊澕鞚� 氍搓磤(line-agnostic)鈥� 頇曥灔霃� 雲检潣欷戩瀰雼堧嫟.
1彀� 旃橂 鞝勲灥歆勳爠: TKI 氙戈步項橃瀽旖旐樃韸胳潣觳� 鞓堧箘雿办澊韯� 氤搓碃; ALK 鞏戩劚 NSCLC鞐愳劀雱澕雼偆敫岇檧鞎岆爥韹半嫏鞚� 牍勱祼頃橂姅 3靸� ALKAZAR 鞁滍棙鞚€ 2025雲� 頃橂皹旮� 齑堨棎霌彪 鞁滌瀾鞓堨爼鞛呺媹雼�.

韴瀽鞛� 鞖旍爯: 欷戩 雼れ 旃橂 頇橃瀽甑办棎靹滌潣頃奠嫭須姤, 歆€靻嶌劚氚� 雵岆偞頇滌劚, RTOR 歆€鞗� NDA 鞚检爼, 攴鸽Μ瓿� 雼れ枒頇旊悳 1彀� 旃橂 臧滊皽瓿勴殟鞚� 瓴绊暕霅橃柎 Nuvalent鞚� 雼赴靸侅梾鞝勲瓿� 瓴届焷鞚� 旃橃棿頃� ROS1/ALK TKI 鞁滌灔雮� 鞝勲灥鞝� 鞙勳箻毳� 臧曧檾頃╇媹雼�.

Nuvalent, Inc. (NASDAQ : NUVL) a d茅pos茅 un formulaire 8-K r茅v茅lant des donn茅es cl茅s de phase 1/2 et des avanc茅es r茅glementaires pour son inhibiteur s茅lectif ROS1 principal, zidesamtinib, dans le cancer du poumon non 脿 petites cellules (NSCLC) ROS1-positif.

Jeu de donn茅es pivot 鈥� patients pr茅trait茅s par TKI (n = 117)

Taux de r茅ponse objective (ORR, RECIST 1.1, BICR) : 44 % (51/117 ; IC 脿 95 % : 34-53).
Durabilit茅 : la probabilit茅 Kaplan-Meier de rester en r茅ponse 鈮�6, 鈮�12 et 鈮�18 mois 茅tait respectivement de 84 %, 78 % et 62 % ; dur茅e m茅diane 茅mergente de la r茅ponse (DOR) de 22,0 mois.
Activit茅 selon les profils de r茅sistance : ORR de 54 % chez les patients avec mutation ROS1 G2032R (n = 26) et 51 % chez ceux avec un seul TKI ant茅rieur (crizotinib ou entrectinib ; n = 55).
Efficacit茅 intracr芒nienne (maladie CNS mesurable au d茅part, n = 56) : IC-ORR 48 % avec 20 % de r茅ponses compl猫tes ; IC-DOR 鈮� 12 mois 脿 71 %.
S茅curit茅 (n = 432 脿 la dose recommand茅e pour la phase 2) : les EIG les plus fr茅quents 鈮�15 % 茅taient 艙d猫me p茅riph茅rique (36 %), constipation (17 %), augmentation de la CPK (16 %), fatigue (16 %), dyspn茅e (15 %) ; r茅ductions de dose 10 %, arr锚ts 2 %.

Donn茅es pr茅liminaires chez les patients na茂fs de TKI (n = 35)

ORR 89 % (31/35) ; DOR 鈮�6 et 鈮�12 mois 脿 96 %.
Sous-groupe intracr芒nien (n = 6) : IC-ORR 83 % avec 67 % de r茅ponses compl猫tes ; aucune progression CNS parmi les r茅pondeurs.
Le recrutement mondial pour la cohorte na茂ve de TKI a atteint 104 patients.

脡tapes r茅glementaires et pipeline

R茅union pr茅-NDA termin茅e ; la FDA a accept茅 d鈥檌nt茅grer la NDA de zidesamtinib dans le programme pilote AG真人官方-Time Oncology Review (RTOR).
Soumission rolling de la NDA pr茅vue pour juillet 2025, avec ach猫vement cibl茅 au T3 2025 ; la soci茅t茅 discute 茅galement d鈥檜ne extension 芦 line-agnostic 禄 avec la FDA.
Progr猫s dans la strat茅gie de premi猫re ligne : premiers r茅sultats pr茅liminaires de la cohorte na茂ve de TKI rapport茅s ; l鈥檈ssai de phase 3 ALKAZAR comparant neladalkib 脿 alectinib dans le NSCLC ALK-positif d茅butera le recrutement d茅but du second semestre 2025.

Points cl茅s pour les investisseurs : L鈥檈fficacit茅 pivot, la durabilit茅 et l鈥檃ctivit茅 intracr芒nienne dans une population fortement pr茅trait茅e, combin茅es 脿 un calendrier NDA facilit茅 par RTOR et un plan de d茅veloppement diversifi茅 en premi猫re ligne, renforcent collectivement les perspectives commerciales 脿 court terme de Nuvalent et son positionnement strat茅gique dans le paysage concurrentiel des TKI ROS1/ALK.

Nuvalent, Inc. (NASDAQ: NUVL) hat eine 8-K eingereicht, in der entscheidende Phase-1/2-Daten und regulatorische Fortschritte f眉r seinen f眉hrenden ROS1-selektiven Inhibitor Zidesamtinib bei ROS1-positivem nicht-kleinzelligem Lungenkrebs (NSCLC) offengelegt werden.

Wichtiges Datenset 鈥� Vorbehandelte TKI-Patienten (n = 117)

Objektive Ansprechrate (ORR, RECIST 1.1, BICR): 44% (51/117; 95 % CI 34-53).
Dauerhaftigkeit: Kaplan-Meier-Wahrscheinlichkeit, mindestens 6, 12 bzw. 18 Monate in Ansprechhaltung zu bleiben, betrug 84 %, 78 % bzw. 62 %; mediane Ansprechdauer (DOR) von 22,0 Monaten im Entstehen.
Aktivit盲t 眉ber Resistenzprofile hinweg: ORR von 54 % bei Patienten mit ROS1 G2032R-Mutation (n = 26) und 51 % bei Patienten mit nur einer vorherigen TKI-Behandlung (Crizotinib oder Entrectinib; n = 55).
Intrakranielle Wirksamkeit (messbare ZNS-Erkrankung zu Studienbeginn, n = 56): IC-ORR 48 % mit 20 % Komplettremissionen; IC-DOR 鈮� 12 Monate bei 71 %.
Sicherheit (n = 432 bei RP2D): h盲ufigste behandlungsbedingte unerw眉nschte Ereignisse (TEAEs) 鈮�15 % waren peripheres 脰dem (36 %), Verstopfung (17 %), CPK-Anstieg (16 %), M眉digkeit (16 %), Dyspnoe (15 %); Dosisreduktionen 10 %, Abbr眉che 2 %.

Vorl盲ufige Daten bei TKI-naiven Patienten (n = 35)

ORR 89% (31/35); DOR 鈮�6 und 鈮�12 Monate bei 96 %.
Intrakranielle Subgruppe (n = 6): IC-ORR 83 % mit 67 % Komplettremissionen; keine ZNS-Progression bei Ansprechern.
Die weltweite Rekrutierung f眉r die TKI-naive Kohorte hat 104 Patienten erreicht.

Regulatorische und Pipeline-Meilensteine

Vor-NDA-Meeting abgeschlossen; FDA hat zugestimmt, die NDA f眉r Zidesamtinib im AG真人官方-Time Oncology Review (RTOR)-Pilotprogramm zu akzeptieren.
Rollierende NDA-Einreichung beginnt im Juli 2025, geplante Fertigstellung im 3. Quartal 2025; das Unternehmen diskutiert zudem eine 鈥瀕inienunabh盲ngige鈥� Erweiterung mit der FDA.
Fortschritte bei der Erstlinientherapie: erste vorl盲ufige Daten aus der TKI-naiven Kohorte berichtet; Phase-3-ALKAZAR-Studie von Neladalkib vs. Alectinib bei ALK-positivem NSCLC startet die Rekrutierung Anfang der zweiten Jahresh盲lfte 2025.

Investoren-Highlights: Die entscheidende Wirksamkeit, Dauerhaftigkeit und intrakranielle Aktivit盲t in einer stark vorbehandelten Population, kombiniert mit einem RTOR-unterst眉tzten NDA-Zeitplan und einem diversifizierten Entwicklungsplan f眉r die Erstlinie, st盲rken gemeinsam Nuvalents kurzfristige kommerzielle Aussichten und strategische Positionierung im wettbewerbsintensiven ROS1/ALK-TKI-Markt.

Positive

Pivotal ORR 44 % and emerging mDOR 22 months in heavily pre-treated ROS1-positive NSCLC population.
High intracranial activity: 48 % IC-ORR with 20 % CRs addresses CNS disease, a critical unmet need.
Favorable safety: only 2 % discontinuations; manageable TEAEs.
FDA AG真人官方-Time Oncology Review acceptance enables faster NDA evaluation; rolling submission starts July 2025.
Strong TKI-na茂ve efficacy: preliminary ORR 89 %, suggesting front-line potential.
Pipeline expansion: Phase 3 ALKAZAR trial of neladalkib to start early H2 2025, adding a second late-stage asset.

Negative

None.

Insights

Pivotal dataset shows durable systemic and CNS efficacy plus clean safety, supporting imminent NDA in ROS1-positive NSCLC.

Zidesamtinib delivered a 44% objective response rate in 117 heavily pre-treated ROS1-positive NSCLC patients. Responses lasted: 鈮�6 mo in 84%, 鈮�12 mo in 78%, and 鈮�18 mo in 62%, with median DOR still maturing at 22 months. Importantly, activity held in the difficult G2032R resistance subset (54% ORR) and in brain metastases: 48% intracranial ORR with 20% complete responses. Safety was manageable; only 2% discontinued and 10% dose-reduced, dominated by grade-mild edema and constipation. Front-line signal is even stronger鈥�89% ORR in 35 TKI-na茂ve patients, hinting at competitive potential versus current standard first-line agents, though these data remain preliminary. Collectively, the efficacy-safety balance meets typical benchmarks regulators seek for targeted lung cancer drugs and differentiates the molecule through CNS penetration and durability across multiple prior TKIs. Investors often watch for exactly this profile before valuing registrational viability.

FDA RTOR acceptance and rolling NDA plan shorten review cycle, signaling high regulatory confidence in the dataset.

The company concluded its pre-NDA meeting with FDA and secured AG真人官方-Time Oncology Review participation. RTOR allows early submission of topline efficacy and safety modules, enabling FDA to begin evaluation before the full dossier arrives. Nuvalent will start the rolling NDA in July 2025 and target completion in Q3 2025, a timeline consistent with accelerated approvals in oncology. Acceptance into RTOR indicates the agency鈥檚 preliminary agreement that the single-arm Phase 2 data could suffice for registration in the pre-treated setting, mitigating the traditional need for a randomized study. Parallel startup of the ALKAZAR Phase 3 trial positions the portfolio for a broader first-line market, but that study remains future-dated and therefore non-determinative for near-term valuation. Overall, the disclosed regulatory milestones reduce approval risk and could pull forward potential U.S. launch timing relative to standard review pathways.

Dataset chiave 鈥� pazienti precedentemente trattati con TKI (n = 117)

Tasso di risposta obiettiva (ORR, RECIST 1.1, BICR): 44% (51/117; intervallo di confidenza 95% 34-53).
Durata: la probabilit脿 Kaplan-Meier di mantenere la risposta per 鈮�6, 鈮�12 e 鈮�18 mesi 猫 stata rispettivamente dell鈥�84%, 78% e 62%; mediana emergente della durata della risposta (DOR) pari a 22,0 mesi.
Attivit脿 attraverso profili di resistenza: ORR del 54% nei pazienti con mutazione ROS1 G2032R (n = 26) e del 51% in quelli con un solo precedente TKI (crizotinib o entrectinib; n = 55).
Efficacia intracranica (malattia CNS misurabile alla baseline, n = 56): ORR intracranica (IC-ORR) del 48% con il 20% di risposte complete; durata della risposta intracranica (IC-DOR) 鈮� 12 mesi al 71%.
Sicurezza (n = 432 alla dose raccomandata per la fase 2): eventi avversi correlati al trattamento (TEAE) pi霉 frequenti 鈮�15% sono stati edema periferico (36%), stitichezza (17%), aumento della CPK (16%), affaticamento (16%), dispnea (15%); riduzioni di dose 10%, interruzioni 2%.

Dati preliminari in pazienti na茂ve a TKI (n = 35)

ORR 89% (31/35); durata della risposta 鈮�6 e 鈮�12 mesi al 96%.
Sottogruppo intracranico (n = 6): IC-ORR 83% con 67% di risposte complete; nessuna progressione CNS tra i responder.
L鈥檃rruolamento globale per la coorte na茂ve a TKI ha raggiunto 104 pazienti.

Traguardi regolatori e pipeline

Incontro pre-NDA completato; FDA ha accettato di includere la NDA di zidesamtinib nel programma AG真人官方-Time Oncology Review (RTOR).
Invio rolling della NDA previsto per luglio 2025, completamento stimato per il terzo trimestre 2025; la societ脿 sta inoltre discutendo con la FDA una possibile espansione 鈥渓ine-agnostic鈥�.
Progressi nella strategia di prima linea: primi dati preliminari dalla coorte na茂ve a TKI riportati; lo studio di Fase 3 ALKAZAR, che confronta neladalkib con alectinib nel NSCLC ALK-positivo, inizier脿 l鈥檃rruolamento nella prima met脿 del 2025.

Conjunto de datos crucial 鈥� pacientes previamente tratados con TKI (n = 117)

Tasa de respuesta objetiva (ORR, RECIST 1.1, BICR): 44% (51/117; intervalo de confianza del 95% 34-53).
Durabilidad: la probabilidad Kaplan-Meier de mantener la respuesta 鈮�6, 鈮�12 y 鈮�18 meses fue del 84%, 78% y 62%, respectivamente; mediana emergente de duraci贸n de la respuesta (DOR) de 22,0 meses.
Actividad en perfiles de resistencia: ORR del 54% en pacientes con mutaci贸n ROS1 G2032R (n = 26) y 51% en aquellos con un solo TKI previo (crizotinib o entrectinib; n = 55).
Eficacia intracraneal (enfermedad CNS medible en l铆nea base, n = 56): IC-ORR 48% con 20% de respuestas completas; IC-DOR 鈮� 12 meses 71%.
Seguridad (n = 432 en RP2D): los eventos adversos relacionados con el tratamiento (TEAE) m谩s frecuentes 鈮�15% fueron edema perif茅rico (36%), estre帽imiento (17%), aumento de CPK (16%), fatiga (16%), disnea (15%); reducciones de dosis 10%, interrupciones 2%.

Datos preliminares en pacientes na茂ve a TKI (n = 35)

ORR 89% (31/35); DOR 鈮�6 y 鈮�12 meses 96%.
Subgrupo intracraneal (n = 6): IC-ORR 83% con 67% de respuestas completas; sin progresi贸n CNS entre respondedores.
La inscripci贸n global para la cohorte na茂ve a TKI ha alcanzado 104 pacientes.

Hitos regulatorios y de pipeline

Reuni贸n pre-NDA completada; FDA acord贸 aceptar la NDA de zidesamtinib en el piloto AG真人官方-Time Oncology Review (RTOR).
La presentaci贸n rolling de la NDA comenzar谩 en julio de 2025, con finalizaci贸n prevista para el tercer trimestre de 2025; la compa帽铆a tambi茅n est谩 discutiendo una expansi贸n 鈥渓ine-agnostic鈥� con la FDA.
Avances en la estrategia de primera l铆nea: primeros datos preliminares del cohorte na茂ve a TKI reportados; el ensayo de Fase 3 ALKAZAR de neladalkib vs. alectinib en NSCLC ALK-positivo comenzar谩 el reclutamiento a principios del segundo semestre de 2025.

頃奠嫭雿办澊韯� 靹疙姼鈥� TKI 旃橂 瓴巾棙鞛� (n = 117)

臧濌磤鞝� 氚橃潙毳�(ORR, RECIST 1.1, BICR): 44% (51/117; 95% 鞁犽甑皠 34-53).
歆€靻嶌劚: Kaplan-Meier 攵勳劃鞐愳劀 6臧滌洈, 12臧滌洈, 18臧滌洈鞚挫儊氚橃潙鞙犾 頇曤鞚€ 臧侁皝 84%, 78%, 62%鞓€鞙茧┌, 欷戧皠氚橃潙歆€靻� 旮瓣皠(DOR)鞚€ 22.0臧滌洈搿� 雮橅儉雮姷雼堧嫟.
雮挫劚頂勲頃勲硠頇滌劚霃�: ROS1 G2032R 霃岇棸氤€鞚� 頇橃瀽(n=26)鞐愳劀 ORR 54%, 鞚挫爠鞐� 頃� 氩堨潣 TKI 旃橂(韥Μ臁绊嫲雼� 霕愲姅鞐旐姼霠夗嫲雼�; n=55)毳� 氚涭潃頇橃瀽鞐愳劀 ORR 51%毳� 旮半頄堨姷雼堧嫟.
雵岆偞須姤(旮办爛靹犾棎靹� 旄§爼臧€電ロ暅欷戩稊鞁犼步瓿� 歆堩櫂, n=56): 雵岆偞 ORR 48%鞐� 20% 鞕勳爠氚橃潙; 12臧滌洈鞚挫儊雵岆偞氚橃潙歆€靻嶋(IC-DOR) 71%.
鞎堨爠靹� (RP2D 鞖╇焿, n=432): 15% 鞚挫儊氚滌儩頃� 欤检殧旃橂 甏€霠� 鞚挫儊氚橃潙(TEAE)鞚€ 毵愳磮攵€膦�(36%), 氤€牍�(17%), CPK 歃濌皜(16%), 頂茧(16%), 順疙潯瓿る瀫(15%)鞚措┌, 鞖╇焿臧愲焿鞚€ 10%, 欷戨嫧鞚€ 2%鞓€鞀惦媹雼�.

TKI 氙戈步項橃瀽鞓堧箘雿办澊韯� (n = 35)

ORR 89% (31/35); 6臧滌洈氚� 12臧滌洈鞚挫儊氚橃潙歆€靻嶋 96%.
雵岆偞頃橃渼攴鸽９ (n = 6): 雵岆偞 ORR 83%鞐� 67% 鞕勳爠氚橃潙; 氚橃潙鞛� 欷� 欷戩稊鞁犼步瓿� 歆勴枆鞐嗢潓.
TKI 氙戈步項橃瀽旖旐樃韸胳潣鞝� 靹戈硠霌彪 頇橃瀽靾橂姅 104氇呾棎霃勲嫭頄堨姷雼堧嫟.

攴滌牅氚� 韺岇澊頂勲澕鞚� 鞚挫爼響�

靷爠 NDA 氙疙寘鞕勲; FDA電� 歆€雿办偧韹半嫏 NDA毳� 鞁れ嫓臧� 膦呾枒頃� 瓴€韱�(RTOR) 韺岇澕霟� 頂勲攴鸽灗鞐� 靾橂澖頃橁赴搿� 霃欖潣頄堨姷雼堧嫟.
2025雲� 7鞗旊秬韯� 靾滌皑鞝� NDA 鞝滌稖鞁滌瀾鞓堨爼, 2025雲� 3攵勱赴鞕勲 氇╉憸; 須岇偓電� FDA鞕€ 鈥滊澕鞚� 氍搓磤(line-agnostic)鈥� 頇曥灔霃� 雲检潣欷戩瀰雼堧嫟.
1彀� 旃橂 鞝勲灥歆勳爠: TKI 氙戈步項橃瀽旖旐樃韸胳潣觳� 鞓堧箘雿办澊韯� 氤搓碃; ALK 鞏戩劚 NSCLC鞐愳劀雱澕雼偆敫岇檧鞎岆爥韹半嫏鞚� 牍勱祼頃橂姅 3靸� ALKAZAR 鞁滍棙鞚€ 2025雲� 頃橂皹旮� 齑堨棎霌彪 鞁滌瀾鞓堨爼鞛呺媹雼�.

Jeu de donn茅es pivot 鈥� patients pr茅trait茅s par TKI (n = 117)

Taux de r茅ponse objective (ORR, RECIST 1.1, BICR) : 44 % (51/117 ; IC 脿 95 % : 34-53).
Durabilit茅 : la probabilit茅 Kaplan-Meier de rester en r茅ponse 鈮�6, 鈮�12 et 鈮�18 mois 茅tait respectivement de 84 %, 78 % et 62 % ; dur茅e m茅diane 茅mergente de la r茅ponse (DOR) de 22,0 mois.
Activit茅 selon les profils de r茅sistance : ORR de 54 % chez les patients avec mutation ROS1 G2032R (n = 26) et 51 % chez ceux avec un seul TKI ant茅rieur (crizotinib ou entrectinib ; n = 55).
Efficacit茅 intracr芒nienne (maladie CNS mesurable au d茅part, n = 56) : IC-ORR 48 % avec 20 % de r茅ponses compl猫tes ; IC-DOR 鈮� 12 mois 脿 71 %.
S茅curit茅 (n = 432 脿 la dose recommand茅e pour la phase 2) : les EIG les plus fr茅quents 鈮�15 % 茅taient 艙d猫me p茅riph茅rique (36 %), constipation (17 %), augmentation de la CPK (16 %), fatigue (16 %), dyspn茅e (15 %) ; r茅ductions de dose 10 %, arr锚ts 2 %.

Donn茅es pr茅liminaires chez les patients na茂fs de TKI (n = 35)

ORR 89 % (31/35) ; DOR 鈮�6 et 鈮�12 mois 脿 96 %.
Sous-groupe intracr芒nien (n = 6) : IC-ORR 83 % avec 67 % de r茅ponses compl猫tes ; aucune progression CNS parmi les r茅pondeurs.
Le recrutement mondial pour la cohorte na茂ve de TKI a atteint 104 patients.

脡tapes r茅glementaires et pipeline

R茅union pr茅-NDA termin茅e ; la FDA a accept茅 d鈥檌nt茅grer la NDA de zidesamtinib dans le programme pilote AG真人官方-Time Oncology Review (RTOR).
Soumission rolling de la NDA pr茅vue pour juillet 2025, avec ach猫vement cibl茅 au T3 2025 ; la soci茅t茅 discute 茅galement d鈥檜ne extension 芦 line-agnostic 禄 avec la FDA.
Progr猫s dans la strat茅gie de premi猫re ligne : premiers r茅sultats pr茅liminaires de la cohorte na茂ve de TKI rapport茅s ; l鈥檈ssai de phase 3 ALKAZAR comparant neladalkib 脿 alectinib dans le NSCLC ALK-positif d茅butera le recrutement d茅but du second semestre 2025.

Wichtiges Datenset 鈥� Vorbehandelte TKI-Patienten (n = 117)

Objektive Ansprechrate (ORR, RECIST 1.1, BICR): 44% (51/117; 95 % CI 34-53).
Dauerhaftigkeit: Kaplan-Meier-Wahrscheinlichkeit, mindestens 6, 12 bzw. 18 Monate in Ansprechhaltung zu bleiben, betrug 84 %, 78 % bzw. 62 %; mediane Ansprechdauer (DOR) von 22,0 Monaten im Entstehen.
Aktivit盲t 眉ber Resistenzprofile hinweg: ORR von 54 % bei Patienten mit ROS1 G2032R-Mutation (n = 26) und 51 % bei Patienten mit nur einer vorherigen TKI-Behandlung (Crizotinib oder Entrectinib; n = 55).
Intrakranielle Wirksamkeit (messbare ZNS-Erkrankung zu Studienbeginn, n = 56): IC-ORR 48 % mit 20 % Komplettremissionen; IC-DOR 鈮� 12 Monate bei 71 %.
Sicherheit (n = 432 bei RP2D): h盲ufigste behandlungsbedingte unerw眉nschte Ereignisse (TEAEs) 鈮�15 % waren peripheres 脰dem (36 %), Verstopfung (17 %), CPK-Anstieg (16 %), M眉digkeit (16 %), Dyspnoe (15 %); Dosisreduktionen 10 %, Abbr眉che 2 %.

Vorl盲ufige Daten bei TKI-naiven Patienten (n = 35)

ORR 89% (31/35); DOR 鈮�6 und 鈮�12 Monate bei 96 %.
Intrakranielle Subgruppe (n = 6): IC-ORR 83 % mit 67 % Komplettremissionen; keine ZNS-Progression bei Ansprechern.
Die weltweite Rekrutierung f眉r die TKI-naive Kohorte hat 104 Patienten erreicht.

Regulatorische und Pipeline-Meilensteine

Vor-NDA-Meeting abgeschlossen; FDA hat zugestimmt, die NDA f眉r Zidesamtinib im AG真人官方-Time Oncology Review (RTOR)-Pilotprogramm zu akzeptieren.
Rollierende NDA-Einreichung beginnt im Juli 2025, geplante Fertigstellung im 3. Quartal 2025; das Unternehmen diskutiert zudem eine 鈥瀕inienunabh盲ngige鈥� Erweiterung mit der FDA.
Fortschritte bei der Erstlinientherapie: erste vorl盲ufige Daten aus der TKI-naiven Kohorte berichtet; Phase-3-ALKAZAR-Studie von Neladalkib vs. Alectinib bei ALK-positivem NSCLC startet die Rekrutierung Anfang der zweiten Jahresh盲lfte 2025.

06/24/2025 - 06:35 AM

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

     Date of Report (Date of earliest event reported): June 24, 2025

    

NUVALENT, INC.

(Exact name of Registrant as Specified in Its Charter)


Delaware	001-40671	81-5112298
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)

One Broadway 14th Floor
Cambridge, Massachusetts		02142
(Address of Principal Executive Offices)		(Zip Code)

     Registrant’s Telephone Number, Including Area Code: (857) 357-7000

    

     Not Applicable

    

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:


Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Class A Common Stock, par value $0.0001 per share	NUVL	The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 8.01 Other Events.

On June 24, 2025, Nuvalent, Inc. (the “Company”) announced positive pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, in tyrosine kinase inhibitor (“TKI”) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (“NSCLC”) from the global ARROS-1 Phase 1/2 clinical trial.

In addition, Nuvalent announced progress on the front-line development strategies for its parallel lead programs in ROS1-positive and ALK-positive NSCLC, including:

•

The first report of preliminary data from the Phase 2 TKI-naïve cohort in its ARROS-1 clinical trial, in which global enrollment is ongoing; and,

•

The advancement of clinical startup activities to support the global initiation of the ALKAZAR Phase 3, randomized, controlled trial. The trial is designed to evaluate neladalkib, a novel ALK-selective inhibitor, versus alectinib, a front-line standard of care, for the treatment of patients with TKI-naïve ALK-positive NSCLC, and the Company expects to begin enrollment early in the second half of 2025.

The Company completed a pre-New Drug Application (“NDA”) meeting with the U.S. Food and Drug Administration (“FDA”) and aligned on its plans to move forward with an NDA submission seeking an indication for the treatment of zidesamtinib for TKI pre-treated patients with locally advanced or metastatic ROS1-positive NSCLC. The FDA agreed to accept the NDA for participation in the AG真人官方-Time Oncology Review (“RTOR”) pilot program, which facilitates earlier submission of topline data to support an earlier start to the FDA’s evaluation of the application. The Company plans to initiate a rolling NDA submission in July 2025 with completion targeted for the third quarter of 2025, and continues to engage with the FDA on potential opportunities for line-agnostic expansion.

Summary of Pivotal Data

Zidesamtinib is being evaluated in ARROS-1, a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors. The recommended phase 2 dose (“RP2D”) for zidesamtinib of 100 mg once daily (“QD”) was determined during the Phase 1 dose-escalation portion of the trial. The ongoing global, single arm, multi-cohort, open label Phase 2 portion is designed to evaluate zidesamtinib at the RP2D with registrational intent for both TKI-naïve and TKI pre-treated patients with advanced ROS1-positive NSCLC.

In this pivotal dataset for the TKI pre-treated ROS1-positive NSCLC population, data are pooled across Phase 1 and 2 and reported for the primary objective of objective response rate (“ORR”, RECIST 1.1) by blinded independent central review (“BICR”). Key secondary objectives include duration of response (“DOR”), intracranial ORR (“IC-ORR”), and safety.

As of the data cut-off date of March 21, 2025, 514 patients with ROS1-positive solid tumors had received zidesamtinib at any starting dose across the Phase 1 and Phase 2 portions of the ARROS-1 clinical trial. Of these, 432 patients with advanced ROS1-positive NSCLC were treated with zidesamtinib at the RP2D.

Efficacy Analysis in TKI Pre-treated Advanced ROS1-positive NSCLC

The primary analysis population consisted of 117 TKI pre-treated patients with advanced ROS1-positive NSCLC with measurable disease who received zidesamtinib at the RP2D by May 31, 2024 with DOR follow-up of at least 6 months available for nearly all responders.

The primary analysis population was distinct from the ROS1 TKI pre-treated populations that have been reported for the current available and investigational ROS1 TKIs:

Patients received a median of 2 prior lines of therapy (range, 1 – 11) and 53% had received prior chemotherapy.

•

47% of patients received crizotinib or entrectinib, the most commonly used front-line TKIs, as their only ROS1 TKI ± prior chemotherapy. Within this subset, 51% of patients received prior crizotinib and 49% of patients received prior entrectinib; 47% of patients received prior chemotherapy.

•

50% of patients had received 2 or more prior ROS1 TKIs ± prior chemotherapy, of which 93% had received prior lorlatinib, repotrectinib, or taletrectinib.

•

36% of patients had a secondary ROS1 resistance mutation, a key driver of disease progression.

•

49% of patients had active CNS disease by BICR, including cases of disease progression following treatment with the brain-penetrant TKIs lorlatinib, repotrectinib, and/or taletrectinib.

Activity was observed across subsets of TKI pre-treated patients, and durability of response was assessed as the probability of patients remaining in response for at least 6, 12 and 18 months by Kaplan-Meier estimate (Table 1). Median duration of response (“mDOR”) continues to mature.

     Table 1.

     All TKI Pre-treated a

     1 prior ROS1 TKI
(crizotinib or entrectinib)
± chemotherapy b

     ORR, % (n/N)
(95% CI)

     44% (51/117) c
(34, 53)

     51% (28/55) d
(37, 65)

    

     % DOR ≥ 6 months e
(95% CI)

     84%
(71, 92)

     93%
(74, 98)

    

     % DOR ≥ 12 months e
(95% CI)

     78%
(62, 88)

     93%
(74, 98)

    

     % DOR ≥ 18 months e
(95% CI)

     62%
(28, 84)

     93%
(74, 98)

    

     G2032R mutation f

    

     ORR, % (n/N)
(95% CI)

     54% (14/26)
(33, 73)

     83% (5/6)
(36, 100)

    

     % DOR ≥ 6 months e
(95% CI)

     79%
(47, 93)

     80%
(20, 97)

    

     % DOR ≥ 12 months e
(95% CI)

     60%
(28, 81)

     80%
(20, 97)

    

     NE = not estimable. 
a The median duration of follow-up was 11.1 months (range 0.2 – 25.6) and mDOR continue to mature. For responders, the emerging mDOR was 22.0 months (95% CI: 17.2, NE) overall and 17.2 months (95% CI: 3.7, NE) for the subset with G2032R. 
b The median duration of follow-up was 11.8 months (range 1.2 – 25.6) and mDOR continue to mature. For responders, the emerging mDOR was 22.0 months (95% CI: 22.0, NE) overall and NE (95% CI: 1.9, NE) for the subset with G2032R. 
c Includes responses observed in patients previously treated with at least 2 prior ROS1 TKIs ± chemotherapy (22/58, ORR = 38%), and in patients previously treated with repotrectinib (8/17, ORR = 47%) or taletrectinib (3/7, ORR = 43%).
d For patients receiving crizotinib only ± chemotherapy, ORR was 68% (19/28) with no progression events among responders. For patients receiving entrectinib only ± chemotherapy, ORR was 33% (9/27) with three progression events among responders.
e  Estimated for responders by Kaplan-Meier analysis.
f ROS1 G2032R mutation identified in local or central testing of blood (“ctDNA”) or tissue.

    

In patients that had measurable CNS lesions by BICR at baseline (n = 56), the IC-ORR was 48% with 20% (11/56) intracranial complete responses (“CR”) and 2 unconfirmed partial responses (“PR”), and IC-DOR ≥ 12 months of 71% (95% CI: 46, 87).

•

In patients that had only received prior crizotinib, which has limited brain penetrance, ± chemotherapy (n = 13), the IC-ORR was 85% with 54% (7/13) intracranial CRs. There was only one CNS progression event among CNS responders.

•

Intracranial responses were also observed in patients previously treated with the brain-penetrant TKIs entrectinib, lorlatinib, repotrectinib or taletrectinib.

Safety Analyses in Advanced ROS1-positive NSCLC

Zidesamtinib demonstrated a well-tolerated safety profile consistent with its ROS1-selective, TRK-sparing design.

In the 432 patients with advanced ROS1-positive NSCLC treated at RP2D as of the data cut-off date, the median duration of exposure was 5 months (range, 0, 32). The most frequent treatment-emergent adverse events (“TEAEs”) occurring in ≥ 15% of patients were peripheral edema (36%), constipation (17%), blood CPK increase (16%), fatigue (16%), and dyspnea (15%).

Dose reductions due to TEAEs occurred in 10% of patients and 2% of patients discontinued treatment due to TEAEs.

Preliminary Data for TKI-Naïve Patients with Advanced ROS1-positive NSCLC

Encouraging preliminary data were available for 35 TKI-naïve patients with advanced ROS1-positive NSCLC treated with zidesamtinib at RP2D as of August 31, 2024. Patients may have received up to one prior line of chemotherapy.

The preliminary ORR was 89% (31/35) and DOR ranged from 1.9+ to 13.9+ months with DOR ≥ 6 months and 12 months of 96% (95% CI: 76, 99). In 6 patients with measurable intracranial lesions, the IC-ORR was 83% (5/6) and the intracranial CR rate was 67% (4/6). The IC-DOR ranged from 4.6+ to 11.1+ months with no CNS progression among responders.

As of June 16, 2025, a total of 104 patients had been enrolled in the ongoing TKI-naïve cohort of the ARROS-1 trial.

Cautionary Note Regarding Forward-Looking Statements

This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the Company's strategy, business plans, and focus; the expected timing of data announcements, clinical trial initiations, FDA submissions and potential product approval; the clinical development programs for zidesamtinib and neladalkib; the potential clinical effects of zidesamtinib and neladalkib; the design and enrollment of the Company's clinical trials, including for the ARROS-1 and ALKAZAR trials their intended pivotal registration-directed design; the potential of the Company's pipeline programs, including zidesamtinib and neladalkib; the implications of data readouts and presentations; timing and content of potential discussions with FDA regarding potential accelerated approval pathways; the Company's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development. The words "may," "might," "will," "could," "would," "should," "expect," "plan," "anticipate," "aim," "goal," "intend," "believe," "expect," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target" or the negative of these terms and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. You should not place undue reliance on these statements or the scientific data presented.

Any forward-looking statements in this Current Report on Form 8-K are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this Current Report on Form 8-K, including, without limitation: risks that the Company may not fully enroll its clinical trials or that enrollment will take longer than expected; unexpected concerns that may arise from additional data, analysis, or results obtained during preclinical studies and clinical trials; the risk that preliminary results of clinical trials may not be predictive of future results from the same or other trials; the risk that results of earlier clinical trials may not be predictive of the results of later-stage clinical trials; the risk that data from our clinical trials may not be sufficient to support registration and that the Company may be required to conduct one or more additional studies or trials prior to seeking registration of zidesamtinib and neladalkib; the occurrence of adverse safety events; risks that the FDA may not approve the Company's potential products on the timelines the Company expects, or at all; risks of unexpected costs, delays, or other unexpected hurdles; risks that the Company may not be able to nominate drug candidates from its discovery programs; the direct or indirect impact of public health emergencies or global geopolitical circumstances on the timing and anticipated timing and results of the Company's clinical trials, strategy, and future operations, including the ARROS-1 trial and the ALKAZAR trial; the timing and outcome of the Company's planned interactions with regulatory authorities; and risks related to obtaining, maintaining, and protecting the Company's intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, as well as any prior and subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent the Company's views only as of today and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.


			Nuvalent, Inc.

Date:	June 24, 2025	By:	/s/ Deborah A. Miller
			Deborah A. Miller, Ph.D. Chief Legal Officer and Secretary

Source:

FAQ

What is the pivotal ORR achieved by Nuvalent's zidesamtinib in pre-treated ROS1-positive NSCLC?

44 % (51/117; 95 % CI 34-53) per blinded independent central review.

When will Nuvalent (NUVL) begin its rolling NDA submission for zidesamtinib?

The company plans to initiate the rolling NDA in July 2025 and complete it in Q3 2025.

How durable were responses to zidesamtinib in the pivotal dataset?

Kaplan-Meier analysis showed 84 % of responders remained in response 鈮�6 months and 78 % 鈮�12 months.

What intracranial efficacy did zidesamtinib demonstrate?

In patients with measurable CNS disease (n = 56), the IC-ORR was 48 % with 20 % complete responses.

What is the efficacy of zidesamtinib in TKI-na茂ve ROS1-positive NSCLC patients?

Preliminary data showed an 89 % ORR (31/35) and DOR 鈮�6 months in 96 % of responders.

What other late-stage program did Nuvalent highlight in the 8-K filing?

The ALKAZAR Phase 3 trial evaluating neladalkib vs. alectinib in ALK-positive NSCLC, with enrollment expected early H2 2025.

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[8-K] Nuvalent, Inc. Reports Material Event

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Item 8.01 Other Events.

FAQ

What is the pivotal ORR achieved by Nuvalent's zidesamtinib in pre-treated ROS1-positive NSCLC?

When will Nuvalent (NUVL) begin its rolling NDA submission for zidesamtinib?

How durable were responses to zidesamtinib in the pivotal dataset?

What intracranial efficacy did zidesamtinib demonstrate?

What is the efficacy of zidesamtinib in TKI-na茂ve ROS1-positive NSCLC patients?

What other late-stage program did Nuvalent highlight in the 8-K filing?

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[8-K] Nuvalent, Inc. Reports Material Event

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Oncology Clinical Analyst positive

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FORM 8-K

Item 8.01 Other Events.

FAQ

What is the pivotal ORR achieved by Nuvalent's zidesamtinib in pre-treated ROS1-positive NSCLC?

When will Nuvalent (NUVL) begin its rolling NDA submission for zidesamtinib?

How durable were responses to zidesamtinib in the pivotal dataset?

What intracranial efficacy did zidesamtinib demonstrate?

What is the efficacy of zidesamtinib in TKI-na茂ve ROS1-positive NSCLC patients?

What other late-stage program did Nuvalent highlight in the 8-K filing?

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