CRB-701 (SYS6002) A Next Generation Nectin-4 Targeting ADC Demonstrates Encouraging Safety and Broader Efficacy in Phase 1 Study in the US and UK Presented at ASCO-GU 2025
Corbus Pharmaceuticals (NASDAQ:CRBP) presented Phase 1 study results for CRB-701 (SYS6002), a next-generation Nectin-4 targeting ADC, at ASCO-GU 2025. The Western study, conducted in the US and UK, mirrored the four highest doses used in the China study and showed comparable safety and PK profiles with no dose-limiting toxicities.
Key findings include: low levels of peripheral neuropathy (4% combined rate), positive clinical responses in urothelial (mUC) and cervical cancer patients, and notably, multiple responses in head and neck squamous cell carcinoma (HNSCC). The Western study enrolled 38 participants across eight tumor types, with 26 evaluable for efficacy. Dose optimization is ongoing at 2.7 mg/kg and 3.6 mg/kg Q3W.
The drug demonstrated encouraging safety with mainly grade 1 or 2 adverse events, and showed efficacy even in tumors with low Nectin-4 expression levels.
Corbus Pharmaceuticals (NASDAQ:CRBP) ha presentato i risultati dello studio di fase 1 per CRB-701 (SYS6002), un ADC di nuova generazione che mira a Nectin-4, durante l'ASCO-GU 2025. Lo studio occidentale, condotto negli Stati Uniti e nel Regno Unito, ha replicato le quattro dosi più elevate utilizzate nello studio in Cina e ha mostrato profili di sicurezza e farmacocinetica comparabili, senza tossicità limitanti per la dose.
I risultati chiave includono: bassi livelli di neuropatia periferica (4% tasso combinato), risposte cliniche positive in pazienti con cancro uroteliale (mUC) e carcinoma cervicale, e, in particolare, molteplici risposte nel carcinoma a cellule squamose della testa e del collo (HNSCC). Lo studio occidentale ha arruolato 38 partecipanti in otto tipi di tumore, con 26 valutabili per efficacia. L'ottimizzazione della dose è attualmente in corso a 2,7 mg/kg e 3,6 mg/kg ogni 3 settimane.
Il farmaco ha dimostrato una sicurezza incoraggiante con principalmente eventi avversi di grado 1 o 2, e ha mostrato efficacia anche in tumori con bassi livelli di espressione di Nectin-4.
Corbus Pharmaceuticals (NASDAQ:CRBP) presentó los resultados del estudio de fase 1 para CRB-701 (SYS6002), un ADC de nueva generación dirigido a Nectin-4, en el ASCO-GU 2025. El estudio occidental, realizado en EE. UU. y el Reino Unido, replicó las cuatro dosis más altas utilizadas en el estudio de China y mostró perfiles de seguridad y farmacocinética comparables, sin toxicidades limitantes de dosis.
Los hallazgos clave incluyen: bajos niveles de neuropatía periférica (tasa combinada del 4%), respuestas clínicas positivas en pacientes con cáncer urotelial (mUC) y cervical, y, notablemente, múltiples respuestas en carcinoma de células escamosas de cabeza y cuello (HNSCC). El estudio occidental incluyó a 38 participantes en ocho tipos de tumores, con 26 evaluables para eficacia. La optimización de dosis está en curso a 2.7 mg/kg y 3.6 mg/kg cada 3 semanas.
El fármaco demostró una seguridad alentadora con principalmente eventos adversos de grado 1 o 2, y mostró eficacia incluso en tumores con bajos niveles de expresión de Nectin-4.
Corbus Pharmaceuticals (NASDAQ:CRBP)는 ASCO-GU 2025에서 Nectin-4를 표적으로 하는 차세대 ADC인 CRB-701 (SYS6002)의 1상 연구 결과를 발표했습니다. 미국과 영국에서 진행된 서구 연구는 중국 연구에서 사용된 네 가지 고용량을 반영했으며, 용량 제한 독성이 없는 안전성과 약리학적 프로필이 유사함을 보여주었습니다.
주요 발견 사항은 다음과 같습니다: 말초 신경병증의 낮은 수준(4% 결합 비율), 요로 상피(mUC) 및 자궁경부암 환자에서의 긍정적인 임상 반응, 그리고 특히 두경부 편평세포암(HNSCC)에서의 다수의 반응입니다. 서구 연구에는 8종의 종양에서 38명의 참가자가 등록되었으며, 그 중 26명이 효능 평가가 가능했습니다. 용량 최적화는 2.7 mg/kg 및 3.6 mg/kg Q3W에서 진행 중입니다.
이 약물은 주로 1등급 또는 2등급의 부작용을 보이며 안전성이 유망하게 나타났고, Nectin-4 발현 수준이 낮은 종양에서도 효능을 보여주었습니다.
Corbus Pharmaceuticals (NASDAQ:CRBP) a présenté les résultats de l'étude de phase 1 pour CRB-701 (SYS6002), un ADC de nouvelle génération ciblant Nectin-4, lors de l'ASCO-GU 2025. L'étude occidentale, menée aux États-Unis et au Royaume-Uni, a reproduit les quatre doses les plus élevées utilisées dans l'étude chinoise et a montré des profils de sécurité et de pharmacocinétique comparables, sans toxicités limitantes de dose.
Les résultats clés incluent : de faibles niveaux de neuropathie périphérique (taux combiné de 4 %), des réponses cliniques positives chez des patients atteints de cancer urotélial (mUC) et cervical, et surtout, plusieurs réponses dans le carcinome épidermoïde de la tête et du cou (HNSCC). L'étude occidentale a inclus 38 participants dans huit types de tumeurs, dont 26 évaluables pour l'efficacité. L'optimisation de la dose est en cours à 2,7 mg/kg et 3,6 mg/kg toutes les 3 semaines.
Le médicament a montré une sécurité encourageante avec principalement des événements indésirables de grade 1 ou 2, et a montré une efficacité même dans des tumeurs avec de faibles niveaux d'expression de Nectin-4.
Corbus Pharmaceuticals (NASDAQ:CRBP) hat die Ergebnisse der Phase-1-Studie zu CRB-701 (SYS6002), einem ADC der nächsten Generation, das auf Nectin-4 abzielt, auf dem ASCO-GU 2025 präsentiert. Die westliche Studie, die in den USA und im Vereinigten Königreich durchgeführt wurde, spiegelte die vier höchsten Dosen wider, die in der Studie in China verwendet wurden, und zeigte vergleichbare Sicherheits- und PK-Profile ohne dosislimitierende Toxizitäten.
Wichtige Ergebnisse sind: niedrige Raten von peripherer Neuropathie (4% kombinierte Rate), positive klinische Reaktionen bei Patienten mit urotelialem (mUC) und zervikalem Krebs sowie bemerkenswerterweise mehrere Reaktionen bei Plattenepithelkarzinom des Kopf-Hals-Bereichs (HNSCC). Die westliche Studie umfasste 38 Teilnehmer aus acht Tumortypen, von denen 26 auf Wirksamkeit bewertet werden konnten. Die Dosisoptimierung läuft derzeit bei 2,7 mg/kg und 3,6 mg/kg alle 3 Wochen.
Das Medikament zeigte ermutigende Sicherheit mit hauptsächlich Grad 1 oder 2 unerwünschten Ereignissen und zeigte Wirksamkeit selbst bei Tumoren mit niedrigen Nectin-4-Expressionsniveaus.
- No dose-limiting toxicities observed in both Western and China studies
- Multiple tumor responses observed in HNSCC (4 PR, 2 SD out of 7 patients)
- Positive responses in mUC and cervical cancer patients
- Lower incidence of ocular adverse events at optimized doses compared to China study (38% vs 66%)
- Longer ADC half-life and lower free-MMAE exposure compared to enfortumab vedotin
- Two mUC patients showed progressive disease in Western study
- Higher rate of skin and subcutaneous disorders in Western study (24%) compared to China study (8%)
Insights
The Phase 1 clinical trial results for CRB-701 represent a significant advancement in the antibody-drug conjugate (ADC) space, particularly in addressing the historical challenges of ADC toxicity profiles. The observed 4% combined rate of peripheral neuropathy across both Western and Chinese studies is notably lower than existing ADC treatments, where rates can exceed 30-50% with current standard-of-care options.
The drug's differentiated safety profile is further evidenced by the 16% combined rate of skin toxicity and improved ocular adverse event profile with preventative protocols. These safety metrics, coupled with the absence of dose-limiting toxicities, suggest a potentially superior therapeutic window compared to existing treatments.
A particularly compelling aspect is the drug's efficacy in head and neck squamous cell carcinoma (HNSCC), with 4 partial responses and 2 stable disease outcomes among 7 evaluable patients. This represents a significant opportunity, as HNSCC has treatment options and affects approximately 66,000 new patients annually in the US alone.
The ability to achieve responses in tumors with low Nectin-4 expression levels aligns with preclinical data and potentially expands the addressable patient population beyond what's currently possible with existing Nectin-4 targeted therapies. The ongoing dose optimization study focusing on 2.7 mg/kg and 3.6 mg/kg cohorts suggests a methodical approach to finding the optimal therapeutic window.
The comparable pharmacokinetic profile between Western and Chinese studies, characterized by longer ADC half-life and lower free-MMAE exposure, validates the drug's consistent performance across different populations and strengthens its potential for global development.
- Study mirrored 4 highest doses used in China dose escalation study presented at ASCO 2024
- Safety, tolerability and PK comparable to China dataset with no DLTs observed in either study
- Low levels of peripheral neuropathy and skin toxicity observed in both studies
- Clinical responses seen in urothelial (mUC) and cervical cancer participants in both studies
- First time targeting of head and neck squamous cell carcinoma (HNSCC) with CRB-701 yields multiple responses
- Dose optimization is underway with dosing at 2.7 mg/kg and 3.6 mg/kg Q3W
NORWOOD, Mass., Feb. 14, 2025 (GLOBE NEWSWIRE) -- Corbus Pharmaceuticals Holdings, Inc. (NASDAQ:CRBP) (“Corbus” or the “Company”), announced that data from its US and UK conducted first-in-human dose escalation clinical study (“Western study”) of CRB-701 (SYS6002) is being presented today at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).
The poster is titled Phase 1 Dose-Escalation Study of Next-Generation Nectin-4 Targeting Antibody-Drug Conjugate CRB-701 (SYS6002) in US and UK Patients with Urothelial Cancer and Other Solid Tumors (Perez, et al) and is being presented today between 11:30 am-12:45 pm PST. The poster will also be available on the Corbus website at the start of the poster presentation.
This Phase 1 Western dose escalation study enrolled participants with metastatic urothelial cancer (mUC) and other solid tumors associated with Nectin-4 expression. These included several tumor types not previously explored in China. Unlike the China study, participants were recruited regardless of their individual Nectin-4 levels. The Western study opened for enrollment in April 2024 and enrollment for dose escalation was completed in October 2024. A December 2024 data cut is being presented (n=38) of whom 26 participants were evaluable for efficacy. The Western study enrolled into the top four dose cohorts used in China (1.8, 2.7, 3.6 and 4.5 mg/kg) and adopted the same Q3W regimen.
The corresponding China Phase 1 first-in-human dose escalation study conducted by the Company’s development partner, CSPC Pharmaceutical Group (“CSPC”), enrolled participants with mUC and other solid tumors. The study opened for enrollment in January 2023 and concluded dose escalation in July 2024. Thirty-seven participants were enrolled and 25 were evaluable at time of April 2024 data cut presented at ASCO 2024. PK and dose expansion cohorts are being enrolled in China by CSPC.
Summary of data:
Safety
- No dose limiting toxicities were encountered during the dose escalation phase of both studies.
- CRB-701 was well tolerated with majority of treatment emergent adverse events being grade 1 or 2 in both studies.
- Notably few cases of peripheral neuropathy or skin rash have been reported to date in either study:
- Peripheral neuropathy: Western study (Grade 1-2:
5% (n=2/38), (Grade 3 or above: zero) was comparable to China study (Grade 1:3% (n=1/37), Grade 2 or above: zero). The combined peripheral neuropathy rate for both studies was4% (n=3/75). - Skin and subcutaneous disorders:
24% (n=9/38) in the Western study compared to8% (n=3/37) in the China study. The combined rate for both studies was16% (12/75) across all dose groups.
- Peripheral neuropathy: Western study (Grade 1-2:
- Ocular adverse events: implementation of a proactive, preventative ocular toxicity protocol in the Western study yielded a lower incidence of ocular adverse events in the 2.7 mg/kg and 3.6 mg/kg (doses selected for optimization) in the Western study (
38% ) compared to the China study (66% ). - A single Grade 4 adverse event occurred in the Western study but was not related to CRB-701.
PK
- PK profile seen in the Western study was comparable to that generated in the China study. CRB-701 demonstrated a longer ADC half-life and lower free-MMAE exposure relative to enfortumab vedotin (EV).
Efficacy
- A total of 26 participants with eight tumor types were evaluable for efficacy at the time of this data cut.
- Responses were observed in several tumor types including previously unexplored HNSCC tumors:
- mUC: Western study (n=4, 1 PR, 1 SD and 2 PD); China study (n=9, ORR
44% ). Both mUC PD participants in the Western study were previously treated with EV. - Cervical: Western study (n=2, 1 CR and 1PD); China study (n=7, ORR
43% ). - HNSCC: Western study (n=7, 4 PR, 2 SD and 1 PD).
- mUC: Western study (n=4, 1 PR, 1 SD and 2 PD); China study (n=9, ORR
Nectin-4
- The Western study did not have a Nectin-4 IHC threshold for inclusion.
- Responses were also observed in participants with low H-scores for Nectin-4.
- Data was in line with the pre-clinical data presented at AACR 2023 demonstrating sustained efficacy even in tumors with low H-scores for Nectin-4.
“I am encouraged by this emerging clinical data and its similarity to what has already been established for CRB-701 in China by our partner CSPC”, stated Dominic Smethurst, Chief Medical Officer of Corbus. “It is gratifying to see that the differentiated safety and tolerability profile has been replicated as have the efficacy signals in both mUC and cervical cancers. A new, previously unexplored potential benefit in HNSCC provides further impetus for us to continue the clinical development of this novel, differentiated ADC.”
“Emerging data for this novel Nectin-4 targeting ADC is promising, particularly for tumor types known to express Nectin-4 such as HNSCC”, stated Dr. Ari Rosenberg, Principal Investigator on this study and Assistant Professor of Hematology and Oncology at the University of Chicago. “There remains a substantial unmet need to not only enhance the targeted delivery of the cytotoxic payload, but also improve tolerability and reduce cumulative toxic effects. I am excited to see further data generated with this MMAE-based ADC.”
The dose optimization phase of the Phase 1 Western study has commenced. Participants are being randomized to the 2.7 mg/kg and 3.6 mg/kg cohorts in HNSCC, cervical and mUC tumors. More cohorts may be added to address additional tumor types.
About CRB-701
CRB-701 (SYS6002) is a next-generation antibody-drug-conjugate (ADC) targeting Nectin-4, that contains a site-specific, cleavable linker and a homogenous drug antibody ratio of 2, using MMAE as the payload. Nectin-4 is a clinically validated, tumor-associated antigen in urothelial cancer.
About Corbus
Corbus Pharmaceuticals Holdings, Inc. is an oncology and obesity company with a diversified portfolio and is committed to helping people defeat serious illness by bringing innovative scientific approaches to well understood biological pathways. Corbus’ pipeline includes CRB-701, a next generation antibody drug conjugate that targets the expression of Nectin-4 on cancer cells to release a cytotoxic payload, CRB-601, an anti-integrin monoclonal antibody which blocks the activation of TGFβ expressed on cancer cells, and CRB-913, a highly peripherally restricted CB1 inverse agonist for the treatment of obesity. Corbus is headquartered in Norwood, Massachusetts. For more information on Corbus, visit corbuspharma.com. Connect with us on X, LinkedIn and Facebook.
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INVESTOR CONTACT:
Sean Moran
Chief Financial Officer
Corbus Pharmaceuticals
smoran@corbuspharma.com
Bruce Mackle
Managing Director
LifeSci Advisors, LLC
bmackle@lifesciadvisors.com
FAQ
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