I-Mab (NASDAQ:NBP) presented updated Phase 1b data for givastomig, an investigational treatment being developed for frontline metastatic gastric and gastroesophageal cancer, citing longer follow-up that the company said strengthened its confidence in the therapy’s durability, safety profile and potential path toward registrational development.
The company said it selected an 8 mg/kg dose of givastomig for further development and has reached agreement with the U.S. Food and Drug Administration on key elements of a global registrational study protocol. The company did not provide a trial-start timeline, saying it is still finalizing its execution plan.
Updated efficacy results
Givastomig combines CLDN18.2 targeting with conditional 4-1BB T-cell activation and is being studied in combination with nivolumab and chemotherapy. Chief Medical Officer Phillip Dennis said the Phase 1b study was intended to identify a registrational dose, assess activity across CLDN18.2 expression levels and evaluate the durability of benefit with longer follow-up.
At the selected 8 mg/kg dose, with nearly 18 months of median follow-up, Dennis reported:
- An objective response rate of 82% among patients with high CLDN18.2 expression, defined as greater than 75%.
- An objective response rate of 75% among patients with CLDN18.2 expression between 1% and 74%.
- A median tumor reduction of 62%.
- Tumor shrinkage in 68 of 69 efficacy-evaluable patients.
- A median duration of response of 15.2 months.
- Median progression-free survival of 16.9 months.
At the data cutoff, 14 patients remained on treatment. Dennis said there had been 13 progression events, while 18 patients remained censored. He added that responses in some patients continued to deepen after the initial response.
“The signal became stronger rather than weaker as follow-up matured,” Dennis said, while noting that the results remain early-phase data.
Safety and dose selection
The company said no Grade 4 or Grade 5 givastomig-related adverse events were observed. The most common treatment-related adverse events were nausea, vomiting and fatigue. Dennis said the principal incremental immune-related toxicity compared with nivolumab plus chemotherapy was gastritis, which he described as generally Grade 2 or lower, with Grade 3 cases occurring infrequently.
At the 8 mg/kg dose, the company reported a 6% incidence of Grade 3 gastritis events. Dennis said the company refined management procedures during the Phase 1b trial, including early recognition, treatment interruption, high-dose steroids and gradual steroid tapering. He said the average duration of Grade 3 gastritis events during the prior year had fallen to less than 10 days.
In response to an analyst question, Dennis said the reported discontinuation rate included early infusion-related reactions that occurred before premedication procedures were implemented. Excluding those patients, he said the discontinuation rate was 16%, while discontinuations attributed to gastritis were 13%. He also said the company had been able to restart givastomig in 67% of patients following a gastritis episode.
Samuel Klempner, an associate professor of medicine at Massachusetts General Hospital and lead investigator in the study, said the 8 mg/kg dose appeared to offer a reasonable balance between efficacy and toxicity. He said both the 8 mg/kg and 12 mg/kg doses showed activity, though the higher dose had numerically higher toxicity, including gastritis.
Clinical perspective and regulatory path
Klempner said the durability findings were particularly notable in frontline treatment, where sustained disease control is more meaningful than tumor shrinkage alone. He also said the early data did not indicate that benefit was confined to a particular CLDN18.2 or PD-L1 biomarker subgroup, though he cautioned that substantially larger patient numbers would be needed to evaluate potential subgroup differences.
He noted that the company’s Phase 1b population included patients across a broad range of CLDN18.2 expression, including lower-expression tumors. Dennis added that 55% of patients at the 8 mg/kg dose had peritoneal metastases, which he characterized as a difficult-to-treat population.
Regarding the registrational program, Dennis said the FDA has aligned with the company on key design elements, including regional distribution and statistical details. The company said it is considering paths to accelerated approval based on objective response rate and progression-free survival, while overall survival would be required for full approval.
Chief Executive Officer Srishti Gupta said the more mature dataset provided the basis for selecting the 8 mg/kg dose and advancing givastomig toward a global registrational study. The company said it expects to provide an update on study timing once planning is finalized.
About I-Mab (NASDAQ:NBP)
I-Mab (NASDAQ: NBP) is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing novel biologic medicines, primarily for the treatment of cancer. Its research and development activities center on immunotherapies designed to activate the immune system or target specific proteins associated with tumor growth and survival.
The company’s pipeline has included investigational antibody-based therapies such as givastomig, a bispecific antibody designed to target Claudin 18.2 and stimulate an immune response through 4-1BB, as well as other programs directed at tumor-associated and immune-regulatory targets.
