Full Dose-Escalation Data Show Continued High Response Rates and Favorable Safety Profile of ISB 2001, a First-in-Class BCMA × CD38 × CD3 Trispecific Antibody, for the Treatment of Relapsed/Refrac...
TRIgnite-1 study shows an overall response rate (ORR) of 74% across nine dose levels, in heavily pretreated patients with a median of six prior lines of therapy
ORR is remarkably high in patients with no prior CAR-T or bispecific therapies (84%) as well as in patients who had received prior T cell- targeted therapies, prior BCMA-targeted therapies, or were refractory to anti-CD38 therapy (range: 71–73%)
Safety profile continues to be favorable, with the majority of patients remaining on treatment at data cutoff
FDA recently granted ISB 2001 Fast Track Designation
NEW YORK, June 2, 2025 /PRNewswire/ -- Ichnos Glenmark Innovation (IGI), a global, fully integrated clinical-stage biotechnology company focused on developing multispecifics™ in oncology, today presented promising full dose-escalation results from its Phase 1 TRIgnite-1 study of ISB 2001, an investigational first-in-class BCMA × CD38 × CD3-targeting trispecific antibody for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). These data, presented as a rapid oral presentation (Abstract #7514) at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, demonstrated a sustained overall response rate (ORR) of 79% and a high complete/stringent complete response (CR/sCR) rate of 30% across seven active dose levels (≥ 50 µg/kg) in a heavily pretreated patient population, with a favorable safety profile. The ORR was 74% in all treated patients, including two patients treated at lower dose levels.
ISB 2001 was designed to simultaneously target multiple myeloma by binding to the tumor- associated antigens BCMA and CD38, even when expressed at low levels, while engaging T cells to trigger an immune response. This novel trispecific design enhances tumor-specific cytotoxicity and aims to overcome resistance mechanisms seen with first-generation bispecific antibodies and CAR T-cell therapies, while minimizing off-tumor toxicity.
Professor Hang Quach, M.D., Professor of Haematology at the University of Melbourne and Director of Haematology at St. Vincent's Hospital Melbourne, said "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."
A total of 35 patients with at least one month of follow-up had received a median of six prior lines of therapy (range: 3–11) at study entry, underscoring a heavily pretreated population. ISB 2001 demonstrated high response rates at active dose levels, with 33 patients treated at ≥ 50 µg/kg (dose levels 3–9). Responses were durable and deepened over time, irrespective of prior lines of therapy or refractoriness status, reinforcing the strength of earlier findings reported at ASH 2024 Annual Meeting in 18 patients treated with ISB 2001 at doses ≥ 50 µg/kg:
- The ORR was 79% (26/33), including a CR/sCR rate of 30% (10/33), with a median follow- up of 6.3 months (range: 1–16).
- Of the 10 patients achieving CR/sCR, eight were evaluable for minimal residual disease (MRD), and six achieved MRD negativity, indicating no detection of myeloma cells by molecular or flow cytometry assays with 10-5 sensitivity, and reinforcing the depth of response.
- Among 25 patients refractory to anti-CD38 therapies, the ORR was 72%, with a CR/sCR rate of 24%.
- In 19 patients without prior T-cell directed therapy (TCDT), including bispecific antibodies and/or CAR T-cell therapy, the ORR was 84%, with CR/sCR rate of 32%.
- Among 14 patients previously treated with TCDT, the ORR remained strong at 71% with a CR/sCR rate of 28%.
- In 15 patients who had received prior BCMA-targeted therapies, the ORR was 73%, with a CR/sCR rate of 27%.
- The median half-life of ISB 2001 was approximately 17 days, supporting the potential for less-frequent dosing.
ISB 2001 demonstrated a favorable safety profile throughout the dose-escalation phase, with no dose-limiting toxicities (DLTs) reported. Cytokine release syndrome (CRS) occurred in 24 patients (69%), primarily Grade 1, with only four patients experiencing Grade 2 events. CRS was mostly limited to the first administration of ISB 2001, and no severe or life-threatening cases were observed. Drug-related severe infections were infrequent (4 patients, 11%), with no Grade 4 or higher infection. One patient experienced Grade 1 ICANS; no other drug-related neurologic adverse events were reported.
The dose-expansion portion of the Phase 1 study is ongoing to establish the recommended Phase 2 dose (RP2D) and the best dosing schedule to enable the first registrational study with ISB 2001.
"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," said Lida Pacaud, M.D., Chief Medical Officer at IGI. "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."
About TRIgnite-1
TRIgnite-1 (NCT05862012) is an ongoing Phase 1, first-in-human, open-label, multicenter study evaluating the safety and anti-myeloma activity of ISB 2001 in patients with RRMM. The dose- escalation study enrolled patients with RRMM who were treated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies and are refractory to, or intolerant of, established therapies known to provide clinical benefit in multiple myeloma. Patients with prior CAR-T cell therapies, bispecifics and/or prior BCMA targeted agents were eligible.
The TRIgnite-1 study has two parts: dose escalation and dose expansion. The dataset presented comes from patients treated in the entire dose-escalation portion who have at least 1-month follow-up at six sites in the United States and Australia. The dose-expansion study is randomized, compliant with Project Optimus at the U.S. Food and Drug Administration (FDA), and is underway in the U.S. and Australia, with European enrollment beginning soon.
About ISB 2001 and Relapsed/Refractory Multiple Myeloma
ISB 2001 is a first-in-class trispecific T-cell engager that targets BCMA and CD38 on myeloma cells and CD3 on T cells. Developed using IGI's proprietary BEAT® protein platform, ISB 2001 was engineered with two distinct binders against myeloma-associated antigens to enhance avidity, even at low target expression levels, while aiming to improve safety over first-generation bispecific antibodies.
The U.S. Food and Drug Administration (FDA) granted ISB 2001 Fast Track Designation in May 2025 and Orphan Drug Designation in July 2023.
Nearly all patients with RRMM ultimately experience disease progression. With no cure currently available and limited treatment options once approved therapies are exhausted, there remains a significant unmet need. IGI is developing ISB 2001 to address this gap, specifically for patients who have previously received T-cell–directed therapies, including CAR T-cell treatments and bispecific antibodies.
About IGI
IGI is a global, fully integrated clinical-stage biotechnology company focused on developing innovative biologics in oncology. Headquartered in New York, NY, IGI is advancing a robust pipeline of novel, first-in-class multispecifics™ aimed at addressing complex diseases and treating patients holistically. Powered by its proprietary BEAT® technology platform, IGI is committed to delivering breakthrough, curative therapies to improve and extend the lives of patients battling hematological malignancies and solid tumors. For more information, visit www.IGInnovate.com
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