I-Mab Presents 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) presented positive Phase 1b dose escalation data for givastomig in combination with nivolumab and mFOLFOX6 at ESMO GI 2025. The study evaluated first-line therapy in Claudin 18.2-positive gastric cancer patients.
Key highlights include a confirmed objective response rate (ORR) of 83% (10/12) at selected doses (8 mg/kg and 12 mg/kg) for the ongoing expansion study. The trial demonstrated efficacy across PD-L1 and CLDN18.2 expression levels, with responses in low-expression tumors. With a median follow-up of 9.0 months, the treatment showed favorable tolerability with minimal Grade 3 adverse events.
The study enrolled 17 U.S. patients across three dose levels (5, 8, and 12 mg/kg), achieving a 71% ORR across all doses and a 100% disease control rate. The longest treatment duration was 13.3 months, with 8 patients remaining on treatment at data cutoff.
I-Mab (NASDAQ: IMAB) ha presentato dati positivi di escalation di dose di Fase 1b per givastomig in combinazione con nivolumab e mFOLFOX6 al congresso ESMO GI 2025. Lo studio ha valutato la terapia di prima linea in pazienti con cancro gastrico positivo a Claudin 18.2.
I punti salienti includono un tasso di risposta obiettiva (ORR) confermato dell'83% (10/12) alle dosi selezionate (8 mg/kg e 12 mg/kg) nello studio di espansione in corso. La sperimentazione ha mostrato efficacia indipendentemente dai livelli di espressione di PD-L1 e CLDN18.2, con risposte anche nei tumori a bassa espressione. Con un follow-up mediano di 9,0 mesi, il trattamento ha evidenziato una buona tollerabilità con eventi avversi di Grado 3 minimi.
Lo studio ha arruolato 17 pazienti negli Stati Uniti su tre livelli di dose (5, 8 e 12 mg/kg), raggiungendo un ORR del 71% su tutte le dosi e un tasso di controllo della malattia del 100%. La durata più lunga del trattamento è stata di 13,3 mesi, con 8 pazienti ancora in trattamento al momento del cutoff dei dati.
I-Mab (NASDAQ: IMAB) presentó datos positivos de la fase 1b de escalada de dosis para givastomig en combinación con nivolumab y mFOLFOX6 en ESMO GI 2025. El estudio evaluó la terapia de primera línea en pacientes con cáncer gástrico positivo para Claudin 18.2.
Los aspectos destacados incluyen una tasa de respuesta objetiva (ORR) confirmada del 83% (10/12) en las dosis seleccionadas (8 mg/kg y 12 mg/kg) del estudio de expansión en curso. El ensayo demostró eficacia independientemente de los niveles de expresión de PD-L1 y CLDN18.2, con respuestas en tumores de baja expresión. Con un seguimiento medio de 9,0 meses, el tratamiento mostró una buena tolerabilidad con eventos adversos de grado 3 mínimos.
El estudio reclutó a 17 pacientes en EE.UU. en tres niveles de dosis (5, 8 y 12 mg/kg), logrando una ORR del 71% en todas las dosis y una tasa de control de la enfermedad del 100%. La duración más larga del tratamiento fue de 13,3 meses, con 8 pacientes aún en tratamiento al corte de datos.
I-Mab (NASDAQ: IMAB)는 ESMO GI 2025에서 nivolumab 및 mFOLFOX6와 병용한 givastomig의 1b상 용량 증강 긍정적 데이터를 발표했습니다. 본 연구는 Claudin 18.2 양성 위암 환자를 대상으로 1차 치료를 평가했습니다.
주요 내용으로는 진행 중인 확장 연구에서 선택된 용량(8 mg/kg 및 12 mg/kg)에서 확인된 객관적 반응률(ORR) 83%(10/12)이 포함됩니다. 본 임상시험은 PD-L1 및 CLDN18.2 발현 수준에 관계없이 효능을 보였으며, 낮은 발현 종양에서도 반응을 나타냈습니다. 중앙 추적 관찰 기간 9.0개월 동안 치료는 최소한의 3등급 이상 부작용으로 우수한 내약성을 보였습니다.
연구는 미국 내 3가지 용량(5, 8, 12 mg/kg)에서 총 17명의 환자를 등록했으며, 모든 용량에서 71% ORR과 100% 질병 조절률을 달성했습니다. 최장 치료 기간은 13.3개월이었고, 데이터 컷오프 시점에 8명이 치료를 계속 받고 있었습니다.
I-Mab (NASDAQ : IMAB) a présenté des données positives de l'escalade de dose de phase 1b pour givastomig en association avec le nivolumab et le mFOLFOX6 lors de l'ESMO GI 2025. L'étude a évalué la thérapie de première ligne chez des patients atteints d'un cancer gastrique positif pour Claudin 18.2.
Les points clés incluent un taux de réponse objective (ORR) confirmé de 83 % (10/12) aux doses sélectionnées (8 mg/kg et 12 mg/kg) pour l'étude d'expansion en cours. L'essai a démontré une efficacité indépendamment des niveaux d'expression de PD-L1 et CLDN18.2, avec des réponses même dans les tumeurs à faible expression. Avec un suivi médian de 9,0 mois, le traitement a montré une bonne tolérance avec peu d'événements indésirables de grade 3.
L'étude a recruté 17 patients américains répartis sur trois niveaux de dose (5, 8 et 12 mg/kg), atteignant un ORR de 71 % sur toutes les doses et un taux de contrôle de la maladie de 100 %. La durée de traitement la plus longue a été de 13,3 mois, avec 8 patients encore sous traitement à la date de coupure des données.
I-Mab (NASDAQ: IMAB) präsentierte positive Phase-1b-Dosiseskalationsdaten für givastomig in Kombination mit Nivolumab und mFOLFOX6 auf dem ESMO GI 2025. Die Studie bewertete die Erstlinientherapie bei Patienten mit Claudin 18.2-positivem Magenkrebs.
Wichtige Highlights sind eine bestätigte objektive Ansprechrate (ORR) von 83 % (10/12) bei ausgewählten Dosen (8 mg/kg und 12 mg/kg) der laufenden Erweiterungsstudie. Die Studie zeigte Wirksamkeit unabhängig von den PD-L1- und CLDN18.2-Expressionsniveaus, mit Ansprechen auch bei Tumoren mit niedriger Expression. Mit einer medianen Nachbeobachtungszeit von 9,0 Monaten zeigte die Behandlung eine gute Verträglichkeit mit minimalen Grad-3-Nebenwirkungen.
Die Studie rekrutierte 17 US-Patienten über drei Dosisebenen (5, 8 und 12 mg/kg) und erreichte eine ORR von 71 % über alle Dosen sowie eine Krankheitskontrollrate von 100 %. Die längste Behandlungsdauer betrug 13,3 Monate, wobei zum Zeitpunkt des Daten-Cutoffs 8 Patienten noch in Behandlung waren.
- High ORR of 83% at selected doses for expansion (8 and 12 mg/kg)
- 100% disease control rate across all dose levels
- Efficacy demonstrated in patients with low PD-L1 and CLDN18.2 expression
- Favorable safety profile with minimal Grade 3 adverse events
- Durable responses with longest treatment duration of 13.3 months
- 12% treatment discontinuation rate due to adverse events
- Six cases of Grade 3/4 treatment-related neutropenia observed
- Study limited to U.S. patients only, potentially affecting global applicability
Insights
I-Mab's givastomig shows impressive 83% response rate in gastric cancer with favorable safety, potentially outperforming existing therapies.
The Phase 1b data for givastomig represents a significant development in gastric cancer treatment. The 83% objective response rate at the selected doses (8 mg/kg and 12 mg/kg) stands out compared to historical response rates for current standard therapies. What makes these results particularly notable is the efficacy across varying levels of CLDN18.2 and PD-L1 expression, suggesting givastomig could benefit a broader patient population than existing targeted therapies.
The 100% disease control rate across all dose levels indicates the drug is effectively preventing disease progression in all treated patients. Equally important is the favorable safety profile - particularly the low incidence of gastrointestinal adverse events, which is crucial for gastric cancer patients who often struggle with these symptoms. The single case of Grade 3 liver enzyme elevation and absence of serious gastrointestinal toxicities suggests a manageable safety profile.
The durability of responses, with patients remaining on treatment up to 13.3 months, suggests potential for meaningful clinical benefit. The dose-dependent induction of soluble 4-1BB confirms the drug's mechanism of action is working as intended, activating T cells to attack the cancer.
While these results are promising, it's important to note this remains a small study (17 patients) with relatively short follow-up. The ongoing expansion cohorts at the selected doses will be critical to confirm these findings in a larger patient population and assess progression-free and overall survival benefits.
I-Mab's givastomig shows competitive efficacy and safety data in gastric cancer, strengthening commercial potential against rivals.
I-Mab's givastomig data represents a potential competitive advantage in the emerging CLDN18.2-targeted therapy landscape. The 83% response rate at expansion doses positions givastomig favorably against competitors in development, including Astellas' zolbetuximab (which achieved ~38% ORR in combination with chemotherapy) and BeiGene's zanidatamab (reported ~75% ORR in HER2+ gastric cancer).
The drug's ability to induce responses in patients with low CLDN18.2 expression (100% response rate in the expansion doses) is particularly significant, as it could substantially expand the addressable patient population beyond what's possible with more restrictive CLDN18.2 requirements of competing therapies.
Gastric cancer represents a substantial market opportunity with over 1 million new cases diagnosed globally each year and limited effective therapies. The favorable safety profile, particularly the low incidence of gastrointestinal side effects, could be a key differentiator for givastomig in this indication.
From a development perspective, these positive results support I-Mab's strategy to rapidly advance givastomig. The planned investor events suggest management confidence in the data. The next critical milestones will be completing the dose expansion phase and initiating pivotal trials.
For I-Mab, givastomig represents a potential flagship asset that could drive significant value. As a precision medicine with a dual mechanism targeting both CLDN18.2 and 4-1BB, it fits well with current oncology treatment paradigms and could command premium pricing if approved.
Data show confirmed ORR of
Median follow-up of 9.0 months as of the updated data cutoff
Responses observed in patients with low PD-L1 and/or CLDN18.2 expression
Company to host investor event on Tuesday, July 8th
ROCKVILLE, Md., July 02, 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 the presentation of positive Phase 1b combination data for givastomig, in combination with nivolumab and mFOLFOX6, at the European Society for Medical Oncology Gastrointestinal Cancers Congress 2025 (ESMO GI 2025) in Barcelona (abstract #388MO). Givastomig is a bispecific antibody targeting Claudin 18.2 and 4-1BB. I-Mab plans to host a virtual investor event on Tuesday, July 8th (register here) to review these data.
The Phase 1b data (NCT04900818) show a confirmed objective response rate (ORR) of
“The positive Phase 1b combination data presented at ESMO GI bolster our confidence in givastomig’s potential to be a best-in-class Claudin 18.2 directed therapy. Givastomig has been well tolerated when combined with immuno-oncology and chemotherapy, has shown a high objective response rate, with rapid onset and durable responses that have deepened over time, supported by consistent pharmacokinetic data and soluble 4-1BB induction,” said Phillip Dennis, MD, PhD, Chief Medical Officer of I-Mab. “In addition, we are optimistic about the results from the 8 mg/kg and 12 mg/kg doses. These doses showed an ORR of
“I am encouraged by the response rates, as well as the deepening of responses over time, demonstrated by the givastomig combination regimen in the Phase 1b dose escalation study that we presented today at ESMO GI. Despite approved therapies, targeted treatment options for gastric cancers continue to be limited. While the data are early, givastomig combination therapy demonstrates a high response rate across Claudin 18.2 and PD-L1 expression levels,” said Samuel J Klempner, MD, Associate Professor of Medicine at Massachusetts General Hospital. “In addition, I have been pleased to observe that givastomig has a favorable overall tolerability profile with a low level of gastrointestinal side effects -- especially important for patients with gastric cancer. I look forward to participating in the ongoing givastomig clinical development program, and hope we may be able to expand the population of patients who may benefit from Claudin 18.2 directed agents.”
Virtual Investor Event:
Register (here) for the Post-ESMO GI 2025 Investor Event to be held on Tuesday, July 8th at 2:00 PM EDT. A replay of the webinar will be accessible on the Events page of the I-Mab website for 90 days.
Fireside Chat Event with Lucid Capital Markets to Recap the Presentation:
Tune in (here) for a fireside chat sponsored by Christopher Liu, PharmD, Managing Director at Lucid Capital Markets that will be accessible today at 2:00pm EDT on the Events page of the I-Mab website. A replay of the fireside chat will be available for 90 days.
ESMO GI Presentation Details:
A full copy of the ESMO GI presentation is available on the Publications and Presentations page of the I-Mab website here.
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 May 15, 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+ IHC staining intensity in ≥
1% of tumor cells), regardless of PD-L1 expression levels - All patients were enrolled at sites within the United States
Efficacy Results:
- Confirmed 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)
- 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 pharmacokinetics (PK) were 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) |
| ORR: % (n) | PD-L1 ≥ 5 | PD-L1 < 5 |
| CLDN18.2 ≥ 75 | 80 (8/10) | 0 (0/2) |
| CLDN18.2 < 75 | 100 (1/1) | 75 (3/4) |
Durability:
- 8 of 17 patients remained on study treatment and the longest treatment duration was 13.3 months as of the data cutoff
- Median follow-up was 9.0 months across all dose levels as of the data cutoff
Safety:
- Treatment-related adverse events (TRAEs) leading to discontinuation of any treatment were
12% (two patients), five patients had progressive disease, two patients withdrew from the study for social reasons - No dose limiting toxicities (DLT) were observed and a maximum tolerated dose (MTD) was not reached
- Common 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
- Four cases of Grade 3 and two cases of Grade 4 treatment-related neutropenia were observed driven by an early restriction on prophylaxis use of G-CSF, which has been subsequently lifted. The neutropenia cases were primarily attributed to mFOLFOX6 in the 8 mg/kg cohorts
- No Grade 5 TRAEs were reported
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
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