FDA Grants ISB 2001 Fast Track Designation in RRMM
Following promising phase 1 data, ISB 2001 has gained fast track designation from the FDA for the treatment of relapsed/refractory multiple myeloma.
US FDA
- The FDA granted ISB 2001 fast track designation for the potential treatment of adult patients with relapsed/refractory multiple myeloma (RRMM).
- This indication is for patients with 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 investigational trispecific antibody therapeutic is currently undergoing evaluation in a phase 1 dose-expansion study.
The FDA has granted ISB 2001, an investigational, first-in-class, trispecific antibody therapy, fast track designation in adult patients with RRMM who have received 3 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1
ISB 2001 is a trispecific T-cell engager that targets BCMA and CD38 on myeloma cells and CD3 on T cells that was developed using the proprietary BEAT® protein platform from Ichnos Glenmark Innovation (IGI). ISB 2001 was previously granted orphan drug designation by the FDA in July 2023.
The FDA’s fast track designation is intended to facilitate the development and accelerate the regulatory review of investigational therapies that are designed to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. This designation enables enhanced communication with the FDA, including more frequent meetings and interactions, and allows for a rolling submission and review of the marketing application. Further, therapies granted fast track designation may also qualify for priority review if they fulfill the necessary criteria.
“A growing number of patients with multiple myeloma have been heavily pretreated, have exhausted currently approved therapies, and continue to face disease progression,” said Cyril Konto, MD, president and chief executive officer of IGI, in a press release. “At IGI, we have long recognized the urgent need for novel treatment options—particularly for patients who have already received first-generation bispecifics or [chimeric antigen receptor (CAR)] T-cell therapies. Our trispecific candidate is designed to enhance tumor targeting while reducing on-target, off-tumor toxicity.”
ISB 2001 is currently being assessed in a phase 1, open-label study in patients with heavily pretreated multiple myeloma.2 The study includes patients with RRMM who have previously been treated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 therapies that were given either in combination or as a single agent and are refractory to, or intolerant of, established therapies known to provide clinical benefit in multiple myeloma. Enrollment was open to patients with an ECOG performance status of 2 or less and those with adequate hematologic, hepatic, renal, and cardiac functions.
Microscopic photorealistic image of mutliple myeloma cells - Generated with Adobe Firefly
In part 1 of the study, the dose-escalation portion of the trial, patients with RRMM were treated with ISB 2001 weekly on days 1, 8, 15, and 22 of each 28-day cycle. Patients were also given an additional step-up dose in cycle 1 on day 4. Notably, the duration of each treatment cycle is 28 days, and patients continued to receive ISB 2001 until disease progression, unacceptable toxicity, or any criterion for stopping the study treatment or patient withdrawal from the study.
In part 2, the dose-expansion portion, additional cohorts will be evaluated to further confirm ISB 2001’s safety and optimal biologically active dose. Patients will be given ISB 2001 until disease progression, unacceptable toxicity, or any criterion for stopping the study treatment or patient withdrawal from the study.
Primary end points of the study include frequency and severity of treatment-emergent adverse events and the number of dose-limiting toxicities (DLTs) during the first 28 days after the first administration of ISB 2001 for part 1. Secondary end points include pharmacokinetics, overall response rate (ORR), complete response (CR) rate, duration of response, time to progression, time to next treatment, time to response, progression-free survival, and overall survival.
At the 2024 American Society of Hematology (ASH) Annual Meeting, data from the first-in-human, phase 1, dose-escalation data portion of the trial were presented, showing a high ORR with durable responses. The agent was also shown to have a favorable safety profile.1,3
Among the 20 heavily pretreated patients enrolled as of October 1, 2024, (median of 6 prior lines of therapy), the ORR across all dose levels (0.005 to 1.2 mg/kg) was 75%.3 In patients treated at active doses (≥0.05 mg/kg; n = 18), the ORR rose to 83%, including a stringent CR rate of 17%, CR rate of 6%, partial response (PR) rate of 11%, and very good PR rate of 50%. The median time to first objective response was 36 days, with responses deepening over time; at data cutoff, 80% of patients remained on treatment.
Looking at the study population, 30% of patients had extramedullary plasmacytomas, 33% (of those assessed) had high-risk cytogenetics, 25% were triple refractory, and 10% were penta-refractory. Additionally, 65% were refractory to their most recent therapy, 45% had received prior bispecific antibodies, 40% had been exposed to anti-BCMA agents, and 10% had undergone CAR-T cell therapy.
For safety, ISB 2001 demonstrated a favorable safety and tolerability profile with no DLTs reported and no adverse events (AEs) leading to treatment discontinuation. Cytokine release syndrome (CRS) was primarily mild, with grade 1 CRS observed in 65% and grade 2 CRS in 10% of patients, lasting a median of 2 days. No cases of immune effector cell-associated neurotoxicity syndrome were observed. Other treatment-emergent AEs included grade 1 injection site reactions in 50% of patients and grade 3 infections in 15%.
Pharmacokinetic analysis revealed dose-proportional exposure with a long half-life exceeding 10 days and low immunogenicity (10% across all doses), supporting potential for less frequent dosing schedules than the current weekly subcutaneous administration. Additionally, pharmacodynamic markers indicated T cell activation, proliferation, and a reduction in soluble BCMA levels in most patients treated at effective doses.
Complete results from the dose-escalation portion of the study are planned to be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.1
“We are honored to receive this fast track designation and look forward to working closely with the FDA to advance our MultispecificTM T-cell engager, with the goal of delivering a first-in-class therapy for patients with relapsed or refractory multiple myeloma,” Konto added in the press release.1
