FDA Gives Fast Track Designation to ISB 2001 in Relapsed/Refractory Myeloma

Developers designed ISB 2001 to target BCMA and CD38 expressed on myeloma cells as well as CD3 on T cells.

The FDA has granted fast track designation to the investigational trispecific T-cell engager ISB 2001 as a treatment for patients with relapsed/refractory multiple myeloma, according to a press release from the developer, Ichnos Glenmark Innovation (IGI).¹ Specifically, the indication includes patients who have received 3 or more prior lines of treatment including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

“A growing number of patients with multiple myeloma have been heavily pretreated, have exhausted currently approved therapies, and continue to [experience] disease progression….Our trispecific candidate is designed to enhance tumor targeting while reducing on-target, off-tumor toxicity,” Cyril Konto, MD, president and chief executive officer at IGI, stated in the press release.¹ “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 relapsed or refractory multiple myeloma.”

Developers designed ISB 2001 to target BCMA and CD38 expressed on myeloma cells as well as CD3 on T cells. The agent includes 2 distinct binders against myeloma-related antigens to enhance avidity, which may improve safety vs first-generation bispecific antibodies.

Data in support of ISB 2001 as a treatment for this patient population came from the dose-escalation portion of a phase 1 study (NCT03022825). Investigators previously presented findings from this trial at the 2024 American Society of Hematology Annual Meeting and Exposition (ASH).²

As of October 1, 2024, the overall response rate (ORR) across 20 evaluable patients was 75% (n = 15/20) at all assessed dose levels. Data also showed a stringent complete response (CR) and CR rate of 20%. Among 18 patients who received an active dose of 0.05 mg/kg or higher, the ORR was 83%, which included a sCR or CR in 22%.

Safety data showed no dose-limiting toxicities, and no patients experienced adverse effects (AEs) leading to treatment discontinuation. Additionally, 65% of patients had grade 1 cytokine release syndrome (CRS), and 10% experienced grade 2 events. The median duration of CRS was 2 days (range, 1-8). Investigators observed no instances of immune cell-associated neurotoxicity syndrome.

“The data presented today on ISB 2001 highlight its remarkable effectiveness as a novel trispecific-antibody T cell engager. These results are among the most impressive I have seen in this patient population,” lead study author Hang Quach, MD, professor of Hematology at the University of Melbourne and Director of Hematology at St Vincent’s Hospital Melbourne, stated in a press release on these findings.³ “ISB 2001 has the potential to revolutionize the treatment landscape for heavily pretreated patients with multiple myeloma who have exhausted currently approved therapies.”

Investigators of this phase 1 study are evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ISB 2001 in patients with relapsed/refractory multiple myeloma. Patients received the agent as weekly subcutaneous doses in 28-day cycles, which included 2 step-up doses on cycle 1, day 1 and cycle 1, day 4 before a full target dose on cycle 1, day 8.

The trial’s primary end points included the frequency and severity of treatment-emergent AEs as well as the number of dose-limiting toxicities within 4 weeks after the first dose of ISB 2001.⁴ Secondary end points included the ORR, CR rate, duration of response, time to progression, time to next treatment, time to response, progression-free survival, and overall survival.

Patients 18 years or older with pathologically confirmed multiple myeloma and an ECOG performance status of 0 to 2 were eligible for enrollment on the study. Having adequate hematologic, hepatic, renal, and cardiac functions was another requirement for study entry.

References

1. Ichnos Glenmark Innovation (IGI) receives U.S. FDA fast track designation for ISB 2001 for relapsed/refractory multiple myeloma. News release. Ichnos Glenmark Innovation. May 5, 2025. Accessed May 5, 2025. https://tinyurl.com/46rc4tvh
2. Quach H, Augustson 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. 2024;144(suppl):1026. doi: 10.1182/blood-2024-208189
3. Ichnos Glenmark Innovation (IGI) presents first clinical data from phase 1 study of trispecific TREAT™ antibody, ISB 2001, showing high overall response rate (ORR) with durable responses and favorable safety profile in patients with heavily pretreated multiple myeloma. News release. Ichnos Glenmark Innovation. December 9, 2024. Accessed May 5, 2025. https://tinyurl.com/mr4kumt5
4. Study of ISB 2001 in relapsed/​refractory multiple myeloma. ClinicalTrials.gov. Updated December 19, 2024. Accessed May 5, 2025. https://tinyurl.com/yb3fwnpt