FDA Grants Fast Track Designation to IBS 2001, An Investigational Trispecific Antibody for Multiple Myeloma

ISB 2001 (Ichnos Glenmark Innovation [IGI]), an investigational trispecific antibody, received fast track designation from the FDA for treatment of heavily pretreated patients with relapsed or refractory multiple myeloma (RRMM) who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The decision is based on data from a phase 1, open-label study (NCT05862012), which are to be presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago.¹

Microscopic view of abnormal plasma cell growth in bone marrow | Image Credit: © Diane - stock.adobe.com

MM treatment has significantly improved over the past 2 decades with the identification of key mutations and development of novel targeted therapies, such as bispecific antibodies (BsAb). BsAbs represent a major advancement in MM treatment, offering a potent, targeted, and rapidly deployable immunotherapy. Despite their success, many patients eventually relapse or become refractory to treatment, underscoring the critical need for continued therapeutic advancements.²

The development of BsAbs has led to the emergence of trispecific antibodies. ISB 2001 is a BCMA- and CD38-targeting, first-in-class trispecific T-cell engager designed to improve safety over first-generation BsAbs. It consists of 2 different binders that increase avidity even at low target expression levels by binding to myeloma-associated antigens. ISB 2001 has demonstrated promising tolerability and a manageable safety profile in a phase 1, first-in-human, multicenter, open-label, dose-escalation and dose-expansion study.^3,4

The trial was conducted in 2 parts: dose escalation (part 1) and dose expansion (part 2). The participants received ISB 2001 as a subcutaneous (SC) injection in 28-day cycles with 2 step-up doses on cycle 1 day 1 (C1D1) and cycle 1 day 4 (C1D4) before administering the full target dose on C1D8. Fourteen patients (median age 66 years; male [57.1%]; white [92.9%]) received at least 1 dose of ISB 2001 as part of a dose-escalation study (doses range: 5 to 600 μg per kg). Patients had previously received a median of 4 treatments (range: 2 to 10), and all had been treated with the 3 major drug classes for multiple myeloma. Nine patients had received all 5 classes, and 3 of those were refractory to all 5.^1,4

The primary end point is the number of dose-limiting toxicities (DLTs) that occur within the first 28 days following the initial research therapy, with additional end points including safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of ISB 2001.^3,4

At the median follow-up of 2.2 months (range: 1.0 to 6.6 months), 12 patients achieved an overall response rate (ORR) of 75%, 8.3% had a stringent complete response that was MRD-negative, 16.7% had a very good partial response, and 50% had a partial response. Responses were seen at doses as low as 50 μg per kg, with a 90% ORR at doses greater than or equal to 50 μg per kg. The median time to response was 36 days (range: 29–57 days), and responses continued to improve over time.^3,4

The safety profile was favorable, with no reported dose-limiting toxicities. Common adverse effects (AE) included grade 1 injection site reactions (7 patients) and grade 1 or 2 cytokine release syndrome (CRS) in 71.4% of patients, which occurred most often after the first dose (64.3%) and less frequently after later doses. CRS typically started 2 days after dosing and lasted about 1.5 days (range: 1 to 4). Notably, there were no cases of ICANS, no patients discontinued treatment due to AEs, and there were no treatment-related deaths.^3,4

"A growing number of patients with [MM] have been heavily pretreated, have exhausted currently approved therapies, and continue to face disease progression," Cyril Konto, MD, president and chief executive officer of IGI, said in a press release. "Our trispecific candidate is designed to enhance tumor targeting while reducing on-target, off-tumor toxicity. We are honored to receive this fast track designation and look forward to working closely with the FDA to advance our Multispecific™ T-cell engager, with the goal of delivering a first-in-class therapy for patients with [RRMM]."³

REFERENCES

1. Study of ISB 2001 in relapsed/​refractory multiple myeloma. Updated December 19, 2024. Accessed May 7, 2025. https://clinicaltrials.gov/study/NCT05862012?cond=Relapsed%2FRefractory%20Multiple%20Myeloma&term=ISB%202001&rank=1

2. Navigating the challenges of bispecific antibodies in relapsed and refractory multiple myeloma. Pharmacy Times. January 27, 2025. Accessed May 7, 2025. https://www.pharmacytimes.com/view/navigating-the-challenges-of-bispecific-antibodies-in-relapsed-and-refractory-multiple-myeloma

3. Ichnos Glenmark Innovation (IGI) receives U.S. FDA fast track designation for ISB 2001 for relapsed/refractory multiple myeloma. PR Newswire. May 5, 2025. Accessed May 7, 2025. https://www.prnewswire.com/news-releases/ichnos-glenmark-innovation-igi-receives-us-fda-fast-track-designation-for-isb-2001-for-relapsedrefractory-multiple-myeloma-302445928.html

4. Quach H, Auguston B, Sia H, et al. First results of a phase 1, first-in-human, dose escalation study of ISB 2001, a BCMAxCD38xCD3 targeting trispecific antibody in patients with relapsed/refractory multiple myeloma (RRMM). Blood. November 5, 2024. Doi:10.1182/blood-2024-208189