New York: Ichnos Glenmark Innovation (IGI), a global, fully integrated clinical-stage biotechnology company focused on developing multispecifics in oncology, has 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 followup 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.”