I-Mab Highlights Positive Givastomig Phase 1b Dose Escalation Data in Combination with Immunochemotherapy in Patients with 1L Gastric Cancers at ESMO GI 2025
I-Mab (NASDAQ: IMAB) announced positive Phase 1b dose escalation data for givastomig in combination with immunochemotherapy for first-line gastric cancer treatment. The study demonstrated an impressive 71% objective response rate (ORR) across all dose levels, with an even higher 83% ORR in the selected dose expansion cohorts (8 and 12 mg/kg).
Key highlights include rapid and deepening responses even in tumors with low PD-L1 and CLDN18.2 expression, with a 100% disease control rate across all three dose levels. The treatment showed a favorable safety profile with mostly Grade 1 or 2 adverse events. The study enrolled 17 treatment-naïve metastatic gastric cancer patients in the U.S., with 8 patients still continuing treatment, the longest duration being 11.3 months.
I-Mab (NASDAQ: IMAB) ha annunciato dati positivi dalla fase 1b di escalation della dose per givastomig in combinazione con immunochemioterapia nel trattamento di prima linea del cancro gastrico. Lo studio ha mostrato un impressionante tasso di risposta obiettiva (ORR) del 71% in tutti i livelli di dose, con un 83% di ORR ancora più elevato nelle coorti di espansione della dose selezionate (8 e 12 mg/kg).
I punti salienti includono risposte rapide e sempre più profonde anche nei tumori con bassa espressione di PD-L1 e CLDN18.2, con un tasso di controllo della malattia del 100% in tutti e tre i livelli di dose. Il trattamento ha mostrato un profilo di sicurezza favorevole, con eventi avversi principalmente di grado 1 o 2. Lo studio ha arruolato 17 pazienti con cancro gastrico metastatico naïve al trattamento negli Stati Uniti, di cui 8 pazienti stanno ancora proseguendo la terapia, con una durata massima di 11,3 mesi.
I-Mab (NASDAQ: IMAB) anunció datos positivos de la fase 1b de escalada de dosis para givastomig en combinación con inmunoquimioterapia para el tratamiento de primera línea del cáncer gástrico. El estudio mostró una impresionante tasa de respuesta objetiva (ORR) del 71% en todos los niveles de dosis, con una ORR del 83% aún mayor en las cohortes de expansión de dosis seleccionadas (8 y 12 mg/kg).
Los aspectos más destacados incluyen respuestas rápidas y cada vez más profundas incluso en tumores con baja expresión de PD-L1 y CLDN18.2, con una tasa de control de la enfermedad del 100% en los tres niveles de dosis. El tratamiento mostró un perfil de seguridad favorable con eventos adversos principalmente de grado 1 o 2. El estudio incluyó a 17 pacientes con cáncer gástrico metastásico sin tratamiento previo en EE. UU., de los cuales 8 pacientes continúan con el tratamiento, con una duración máxima de 11,3 meses.
I-Mab (NASDAQ: IMAB)은 1차 위암 치료를 위한 면역화학요법과 병용한 givastomig의 1b상 용량 증량 연구에서 긍정적인 데이터를 발표했습니다. 연구 결과 모든 용량군에서 71%의 객관적 반응률(ORR)을 보였으며, 선택된 용량 확장 코호트(8 및 12 mg/kg)에서는 83%의 ORR을 나타냈습니다.
주요 내용으로는 PD-L1 및 CLDN18.2 발현이 낮은 종양에서도 빠르고 심층적인 반응을 보였으며, 세 가지 용량군 모두에서 100% 질병 조절률을 달성했습니다. 치료는 주로 1~2등급의 이상반응으로 안전성 프로파일이 우수했습니다. 미국에서 치료 경험이 없는 전이성 위암 환자 17명이 등록되었으며, 8명은 여전히 치료를 받고 있고 최장 치료 기간은 11.3개월입니다.
I-Mab (NASDAQ : IMAB) a annoncé des données positives de la phase 1b d'escalade de dose pour givastomig en combinaison avec une immunochimiothérapie pour le traitement de première ligne du cancer gastrique. L'étude a démontré un taux de réponse objective (ORR) impressionnant de 71% à tous les niveaux de dose, avec un taux encore plus élevé de 83% ORR dans les cohortes d'expansion de dose sélectionnées (8 et 12 mg/kg).
Les points clés incluent des réponses rapides et approfondies même dans les tumeurs à faible expression de PD-L1 et CLDN18.2, avec un taux de contrôle de la maladie de 100% sur les trois niveaux de dose. Le traitement a montré un profil de sécurité favorable avec principalement des événements indésirables de grade 1 ou 2. L'étude a inclus 17 patients atteints de cancer gastrique métastatique naïfs de traitement aux États-Unis, dont 8 patients poursuivent encore le traitement, la durée la plus longue étant de 11,3 mois.
I-Mab (NASDAQ: IMAB) gab positive Daten aus der Phase-1b-Dosissteigerungsstudie von Givastomig in Kombination mit Immunchemotherapie zur Erstlinienbehandlung von Magenkrebs bekannt. Die Studie zeigte eine beeindruckende objektive Ansprechrate (ORR) von 71% über alle Dosierungsstufen hinweg, mit einer sogar noch höheren ORR von 83% in den ausgewählten Dosis-Erweiterungskohorten (8 und 12 mg/kg).
Wichtige Highlights sind schnelle und sich vertiefende Ansprechraten, selbst bei Tumoren mit niedriger PD-L1- und CLDN18.2-Expression, sowie eine 100%ige Krankheitskontrollrate über alle drei Dosisstufen. Die Behandlung zeigte ein günstiges Sicherheitsprofil mit überwiegend Nebenwirkungen vom Grad 1 oder 2. In der Studie wurden 17 therapienaive Patienten mit metastasiertem Magenkrebs in den USA eingeschlossen, von denen 8 Patienten die Behandlung weiterhin erhalten, wobei die längste Behandlungsdauer 11,3 Monate beträgt.
- Strong 71% objective response rate (ORR) across all dose levels, increasing to 83% in selected dose expansion cohorts
- 100% disease control rate achieved across all three dose levels
- Favorable safety profile with mostly Grade 1-2 adverse events and no Grade 4-5 TRAEs
- Effective even in patients with low PD-L1 and CLDN18.2 expression, showing 100% response rate in CLDN-Low patients at selected doses
- Responses were rapid and continued to deepen over time
- Study size is relatively small with only 17 patients
- Data is still early stage (Phase 1b)
- Some patients experienced Grade 3 adverse events including abdominal pain, ALT/AST increases, gastritis, and infusion-related reactions
Insights
Strong Phase 1b givastomig data shows 71% response rate in gastric cancer with excellent safety profile, advancing I-Mab's promising oncology asset.
The Phase 1b results for givastomig represent encouraging news for I-Mab's clinical program in gastric cancer. The 71% objective response rate across all dose levels and 83% response rate at the selected expansion doses (8 and 12 mg/kg) demonstrate strong anti-tumor activity in this difficult-to-treat cancer population.
What's particularly notable is the drug's ability to elicit responses in patients with low PD-L1 and low CLDN18.2 expression levels. Typically, checkpoint inhibitors like nivolumab show diminished efficacy in PD-L1 low patients, while most CLDN18.2-targeted therapies require high expression levels. Givastomig's performance in these biomarker-low subgroups suggests it may address an important unmet need for patients who wouldn't qualify for other targeted therapies.
The safety profile appears favorable, with mostly Grade 1-2 adverse events and rare Grade 3 events attributed to givastomig. No Grade 4-5 events or dose-limiting toxicities were reported, which is promising for a combination therapy that includes both immunotherapy and chemotherapy.
The 100% disease control rate across all dose levels further supports givastomig's potential. The pharmacodynamic data showing dose-dependent induction of soluble 4-1BB confirms the drug's mechanism is working as intended, activating T cells to attack the tumor.
While these are early-stage results from a small patient population (n=17), the consistency of response across different dose levels and patient subgroups provides a solid foundation for the ongoing expansion study. The fact that responses deepened over time also suggests durable anti-tumor activity, though longer follow-up will be needed to assess progression-free and overall survival benefits.
Responses observed in patients with low PD-L1 and/or CLDN18.2 expression
Updated results to be presented at ESMO GI on July 2nd
Company to host investor event on July 8th
ROCKVILLE, Md., June 26, 2025 (GLOBE NEWSWIRE) -- I-Mab (NASDAQ: IMAB) (the “Company”), a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer, today announced publication of ESMO Gastrointestinal Cancers Congress 2025 (ESMO GI 2025) abstract #388MO related to positive data from a Phase 1b study evaluating givastomig in combination with nivolumab and mFOLFOX6 chemotherapy for metastatic gastric cancers. An objective response rate (ORR) of
The abstract is based on the results of the dose escalation part of a Phase 1b study (NCT04900818) evaluating the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of givastomig used in combination with nivolumab and mFOLFOX6 as first line therapy (1L) in patients with Claudin 18.2-positive gastric cancers (≥1+ intensity in ≥
“We are excited to share positive initial data from the Phase 1b dose escalation study of givastomig in gastric cancers at ESMO GI 2025. Givastomig shows promising activity in the first line setting, with responses that are both rapid onset and durable, deepening over time. This is the first study to evaluate givastomig in combination with immunochemotherapy and we are very pleased by the overall tolerability, consistent pharmacokinetic data and soluble 4-1BB induction. We look forward to sharing the data with the oncology and investment communities at ESMO GI 2025 on July 2nd,” said Phillip Dennis, MD, PhD, Chief Medical Officer of I-Mab.
“Givastomig's strong response data and favorable safety profile are encouraging. I look forward to presenting the data for this novel Claudin 18.2 targeted therapy next week at ESMO GI and discussing with colleagues,” said Samuel J Klempner, MD, Associate Professor of Medicine at Massachusetts General Hospital. “Gastroesophageal cancers continue to be a significant unmet medical need, and novel combination approaches are critical. On behalf of the study team, I am enthusiastic to continue to support the givastomig clinical program.”
ESMO GI Presentation Details:
Title: Preliminary Safety and Efficacy of Givastomig, a Novel Claudin 18.2/4-1BB Bispecific Antibody, in Combination with Nivolumab and mFOLFOX in Metastatic Gastroesophageal Carcinoma (mGEC)
Speaker: Samuel J. Klempner, MD, Associate Professor of Medicine, Massachusetts General Hospital
Presentation Number: 388MO
Date and Time: Wednesday, July 2nd at 16:50 CEST (10:50am EST)
Givastomig Phase 1b Dose Escalation Data Summary in 1L Gastric Cancers
- 17 advanced metastatic gastric cancer patients were treated with givastomig across the 5 mg/kg (n=5), 8 mg/kg (n=6), and 12 mg/kg (n=6) dose levels as of the February 28, 2025, data cutoff. All patients were efficacy evaluable
Patient Characteristics:
- The 17 patients enrolled in the study were treatment naïve metastatic gastric, esophageal or gastroesophageal adenocarcinomas
- Patients were HER2-negative, Claudin 18.2-positive (defined as >1+ intensity in >
1% of tumor cells) regardless of PD-L1 expression levels - All patients were enrolled at sites within the United States
Efficacy Results:
- Objective Response Rates (ORRs):
71% of patients (12/17) achieved a partial response (PR) per RECIST v1.1- 5 mg/kg (2/5)
- 8 mg/kg (5/6)
- 12 mg/kg (5/6), with one unconfirmed response as of the data cutoff
- At the doses selected for dose expansion (8 and 12 mg/kg),
83% (10/12) of patients achieved PRs 80% of patients (4/5) with CLDN18.2 expression below75% (CLDN-Low) achieved a PR. The CLDN-Low response rate increased to100% of patients (3/3) in the doses selected for expansion (8 and 12 mg/kg)
- The disease control rate (DCR) was
100% across the three dose levels - Dose-dependent PK was observed, similar to monotherapy PK.
- Patients also experienced a dose dependent induction of soluble 4-1BB, a positive indicator of T cell activation and engagement
| ORR: % (n) | All (n=17) | Cohorts Chosen for expansion (8 and 12 mg/kg) (n=12) |
| PD-L1 | ||
| Any | 71 (12/17) | 83 (10/12) |
| ≥5 | 82 (9/11) | 89 (8/9) |
| <5 | 50 (3/6) | 67 (2/3) |
| ≥1 | 73 (11/15) | 82 (9/11) |
| <1 | 50 (1/2) | 100 (1/1) |
| CLDN18.2 | ||
| ≥75 | 67 (8/12) | 78 (7/9) |
| <75 | 80 (4/5) | 100 (3/3) |
Durability:
- 8 of 17 patients remained on study treatment and the longest treatment duration was 11.3 months as of the data cutoff
Safety:
- No dose limiting toxicities (DLT) were observed and a maximum tolerated dose (MTD) was not reached
- Common treatment related adverse events (TRAEs, ≥
10% of patients) were generally Grade 1 or Grade 2 including nausea, vomiting, infusion related reaction, fatigue, decreased appetite, diarrhea, abdominal pain, chills, dyspepsia and gastritis - Grade 3 TRAEs attributed to givastomig were rare, with single cases of abdominal pain, ALT/AST increases, gastritis, and infusion related reaction
- No Grade 4 or Grade 5 TRAEs were reported
Virtual Investor Event:
Register for the Post-ESMO GI 2025 Investor Event here. A replay of the webinar will be accessible on the News & Events page of the I-Mab website for 90 days.
About Givastomig
Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 (CLDN18.2)-positive tumor cells. It conditionally activates T cells through the 4-1BB signaling pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig is being developed for first line (1L) metastatic gastric cancers, with further potential in other solid tumors. In Phase 1 trials, givastomig has shown promising anti-tumor activity attributable to a potential synergistic effect of proximal interaction between CLDN18.2 on tumor cells and 4-1BB on T cells in the tumor microenvironment, while minimizing toxicities commonly seen with other 4-1BB agents.
An ongoing Phase 1b study is evaluating givastomig for the treatment of gastric cancer in the 1L setting in combination with standard of care, nivolumab (an anti-PD-1 checkpoint inhibitor) plus chemotherapy, in dose escalation and dose expansion cohorts. Dose escalation is complete, and enrollment in the first dose expansion cohort (n=20) finished ahead of schedule. Enrollment continues to progress ahead of schedule in the second dose expansion cohort (n=20). The study builds on positive Phase 1 monotherapy data.
Givastomig is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding Greater China and South Korea, equally with ABL Bio.
About I-Mab
I-Mab (NASDAQ: IMAB) is a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer. The Company’s differentiated pipeline is led by givastomig, a potential best-in-class, bispecific antibody (Claudin 18.2 x 4-1BB) designed to treat Claudin 18.2-positive gastric cancers. Givastomig conditionally activates T cells via the 4-1BB signaling pathway in the tumor microenvironment where Claudin 18.2 is expressed. Givastomig is being developed for first-line metastatic gastric cancers, with additional potential in other solid tumors. In Phase 1 trials, givastomig was observed to maintain strong tumor-binding and anti-tumor activity, attributable to a potential synergistic effect of proximal interaction with Claudin 18.2 and 4-1BB, while minimizing toxicities commonly seen with other 4-1BB agents.
For more information, please visit www.i-mabbiopharma.com and follow us on LinkedIn and X.
I-Mab Forward-Looking Statements
This announcement contains forward-looking statements. These statements are made under the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as “will”, “expects”, “believes”, “designed to”, “anticipates”, “future”, “intends”, “plans”, “potential”, “estimates”, “confident”, and similar terms or the negative thereof. I-Mab may also make written or oral forward-looking statements in its periodic reports to the U.S. Securities and Exchange Commission (the SEC), in its annual report to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about I-Mab’s beliefs and expectations, are forward-looking statements. Forward-looking statements in this press release include, without limitation, statements regarding: the Company’s pipeline and clinical development of I-Mab’s drug candidates, including givastomig; the projected advancement of the Company’s portfolio and anticipated milestones and related timing; the Company’s expectations regarding the impact of data from ongoing and future clinical trials; the timing and progress of studies and trials (including with respect to patient enrollment); the potential benefits of givastomig; and the availability of data and information from ongoing studies and trials. Forward-looking statements involve inherent risks and uncertainties that may cause actual results to differ materially from those contained in these forward-looking statements, including but not limited to the following: I-Mab’s ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may or may not support further development or New Drug Application/Biologics License Application (NDA/BLA) approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of I-Mab’s drug candidates; I-Mab’s ability to achieve commercial success for its drug candidates, if approved; I-Mab’s ability to obtain and maintain protection of intellectual property for its technology and drugs; I-Mab’s reliance on third parties to conduct drug development, manufacturing and other services; and I-Mab’s limited operating history and I-Mab’s ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates, as well as those risks more fully discussed in the “Risk Factors” section in I-Mab’s annual report on Form 20-F filed with the SEC on April 3, 2025, as well as the discussions of potential risks, uncertainties, and other important factors in I-Mab’s subsequent filings with the SEC. All forward-looking statements are based on information currently available to I-Mab. I-Mab undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law.
I-Mab Investor & Media Contacts
| PJ Kelleher | |
| LifeSci Advisors | |
| +1-617-430-7579 | |
| pkelleher@lifesciadvisors.com | |
| IR@imabbio.com |
FAQ
What were the key results from I-Mab's Phase 1b givastomig trial for gastric cancer?
How effective was givastomig in patients with low biomarker expression?
What safety concerns were identified in IMAB's givastomig Phase 1b trial?
How many patients were enrolled in the I-Mab givastomig Phase 1b trial?
What is the current status of patients in IMAB's givastomig trial?
