IGI reports phase 1 results of ISB 2001 trispecific antibody in relapsed or refractory multiple myeloma

Ichnos Glenmark Innovation (IGI), a global clinical-stage biotechnology company, has announced full dose-escalation results from its Phase 1 TRIgnite-1 study evaluating ISB 2001, a first-in-class trispecific antibody targeting BCMA × CD38 × CD3 in patients with relapsed or refractory multiple myeloma (RRMM).

The findings were presented as a rapid oral presentation at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting. The data showed an overall response rate (ORR) of 79 per cent and a complete or stringent complete response (CR/sCR) rate of 30 per cent across seven active dose levels (≥ 50 µg/kg). Among all treated patients, including those given lower doses, the ORR was 74 per cent.

Thirty-five patients with a median of six prior lines of therapy (range: 3–11) were enrolled in the study, which highlights the advanced disease profile of the cohort. Thirty-three patients received ISB 2001 at active dose levels of 50 µg/kg or higher.

The study reported that 79 per cent of patients (26 out of 33) achieved a response at these active dose levels. Of these, 10 patients (30 per cent) reached CR/sCR. Eight of these 10 patients were evaluated for minimal residual disease (MRD), with six achieving MRD negativity, measured by assays with a 10^-5 sensitivity.

The ORR was 72 per cent among 25 patients refractory to anti-CD38 therapies, with a CR/sCR rate of 24 per cent. Among the 19 patients without prior T-cell directed therapy (TCDT), which includes bispecific antibodies and CAR T-cell therapy, the ORR was 84 per cent and the CR/sCR rate was 32 per cent. In the 14 patients who had received prior TCDT, the ORR was 71 per cent with a CR/sCR rate of 28 per cent. For 15 patients with prior exposure to BCMA-targeted therapies, the ORR was 73 per cent and the CR/sCR rate was 27 per cent.

The median half-life of ISB 2001 was approximately 17 days, supporting the possibility of extended dosing intervals.

No dose-limiting toxicities were reported during the dose-escalation phase. Cytokine release syndrome (CRS) occurred in 24 patients (69 per cent), mostly Grade 1, with four Grade 2 cases. CRS events were largely limited to the first dose. Drug-related severe infections were reported in four patients (11 per cent) and were all below Grade 4. One patient experienced Grade 1 ICANS, with no other neurologic adverse events attributed to the drug.

Professor Hang Quach, M.D., Professor of Haematology at the University of Melbourne and Director of Haematology at St. Vincent’s Hospital Melbourne, commented, “Responses to ISB 2001 highlight the remarkable anti-myeloma activity of this first-in-class anti-BCMA × CD38 × CD3 trispecific antibody-T cell engager in heavily pretreated RRMM patients, including those who have exhausted prior T cell-redirecting, BCMA-targeted, or anti-CD38 therapies – an especially challenging, quad-exposed patient population. With its unprecedented potency and tolerability, ISB 2001 has the potential to redefine the treatment landscape for RRMM, offering new hope for patients with limited therapeutic options.”

Lida Pacaud, M.D., Chief Medical Officer at IGI, stated, “The high response rates and low safety concerns demonstrated in the dose-escalation portion of the TRIgnite-1 study, conducted in a heavily pretreated population across multiple types of therapies, reinforce the promise of ISB 2001 as a potential new treatment for patients. As we advance to the second part of the TRIgnite-1 study, our focus is now on defining the recommended dosing schedule and evaluating ISB 2001 in a larger population of heavily pretreated RRMM patients, where we hope to observe similarly impressive treatment responses and tolerability.”

The dose-expansion portion of the Phase 1 study is ongoing. IGI is now focused on determining the recommended Phase 2 dose (RP2D) and an appropriate dosing schedule to support further clinical development.