Glenmark’s myeloma drug delivers high response in phase-1 trial

Glenmark

Ichnos Glenmark Innovation (IGI), part of Glenmark on Monday said its novel trispecific antibody, ISB 2001, demonstrated deep and durable responses in relapsed or refractory multiple myeloma (RRMM) in the Phase 1 dose-escalation studies.

ISB 2001 is designed to bind to three different targets or antigens - BCMA, CD38, and CD3.

The company presented the data at the 2025 ASCO Annual Meeting in Chicago.

The study, conducted across six U.S. and Australian centers, enrolled 35 heavily pretreated patients who had already failed a median of six prior therapies—including CAR-T, bi-specifics, and anti-CD38 agents.

“Responses to ISB 2001 highlight its remarkable anti-myeloma activity, even in quad-exposed patients,” said Professor Hang Quach, Director of Hematology at St. Vincent’s Hospital Melbourne. “With unprecedented potency and tolerability, ISB 2001 has the potential to redefine the treatment landscape for RRMM.”

At active dose levels (≥ 50 µg/kg), 26 of 33 evaluable patients (79%) achieved objective responses, including stringent or complete remissions in 30%. Very good partial responses or better (≥ VGPR) were seen in 64%. Among 10 patients who reached CR/sCR, eight were assessed for minimal residual disease (MRD) at a 10⁻⁵ sensitivity, and six (75%) were MRD-negative. The median duration of response has not yet been reached (DOR at interim analysis), with a six-month DOR estimate of 90%.

“Deep and durable responses at ISB 2001 doses of 50 µg/kg and above were encouraging, with most responders still on treatment,” said Lida Pacaud, IGI’s Chief Medical Officer. “Our goal in Part 2 is to identify the optimal Phase 2 dose and dosing schedule.”

Notably, the ORR remained high regardless of prior T-cell redirecting therapies: patients without any prior CAR-T or bispecific exposure (n = 19) saw an 84% ORR; those who had already received T-cell targeted agents (n = 14) had a 71% ORR. Patients refractory to anti-CD38 therapies (n = 25) achieved a 72% ORR, and those previously treated with BCMA-targeted modalities (n = 15) posted a 73% ORR. Responses were also observed in high-risk cytogenetic and extramedullary disease subgroups.

No dose-limiting toxicities (DLTs) emerged up to the 2,700 µg/kg highest dose. Cytokine release syndrome (CRS) occurred in 69% of patients but was almost exclusively Grade 1 (57%) or Grade 2 (11%) and confined to the initial step-up doses. Median time to CRS onset was two days, and median CRS duration was two days. Only one Grade 1 ICANS event was recorded; no Grade 3+ neurologic adverse events occurred. Hematologic toxicities, including neutropenia (49% Grade 3+) and thrombocytopenia (14% Grade 3+), were mostly manageable with standard supportive care.

“ISB 2001’s safety profile—even with frequent weekly subcutaneous dosing—was remarkably clean,” said Eben Lichtman, trial co-investigator at UNC Lineberger. “Low-grade CRS was manageable without routine steroid prophylaxis, enabling patients to continue therapy uninterrupted.”

One unrelated Grade 5 cardiac arrest occurred in a patient with significant cardiovascular history; four severe (Grade 3+) infections were reported (11%), with no Grade 4+ infectious events. No discontinuations were attributed to CRS or neurologic issues.

ISB 2001 displayed dose-proportional pharmacokinetics, with a median half-life of 17 days—supporting the potential for less-frequent dosing intervals in later stages. All 35 patients received step-up priming doses on Days 1 and 4, followed by weekly subcutaneous injections.

The Phase 1 dose-escalation cohort has been fully enrolled, and Part 2 (dose expansion) has commenced under the FDA’s Project Optimus guidelines. Approximately 80 additional RRMM patients will be randomized to varying dosing schedules to determine the recommended Phase 2 dose (RP2D). European enrollment for Part 2 is slated to begin in the third quarter.

“Our objective now is to define the best regimen to maximize efficacy while preserving tolerability,” said Lida Pacaud. “We anticipate that Part 2 will confirm ISB 2001’s potential as a new standard in heavily pretreated myeloma.”

On June 2, Glenmark Pharmaceuticals announced that the USFDA granted Fast Track designation to ISB 2001, reflecting high unmet need in RRMM, particularly for patients who have exhausted CAR-T and first-generation bispecific options. The agent also holds Orphan Drug Status, awarded in July 2023.

Analysts estimate the global RRMM market at over $10 billion by 2028, driven by an aging population and increasing prevalence of refractory subtypes. If ISB 2001 advances through Phase 2/3 with similarly high response rates, it could capture a significant share of late-line therapy revenue.