FDA Grants RMAT Designation to TSC-100 and TSC-101 for Hematologic Malignancies

• The FDA has granted regenerative medicine advanced therapy (RMAT) designation to TSC-100 and TSC-101.

• This designation is intended for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT) with reduced intensity conditioning.

• Findings from the ALLOHA trial (NCT05473910) support this regulatory decision.

The FDA has granted RMAT designation to TSC-100 and TSC-101 for the treatment of patients with hematologic malignancies, including AML, ALL, and MDS, who are undergoing allogeneic HCT with reduced intensity conditioning.¹

The RMAT designation is a specialized program aimed at expediting the development and review processes for promising agents, including gene and cell therapies.

This designation offers intensive FDA guidance for efficient drug development, allowing for early interactions with the FDA to discuss surrogate or intermediate end points, potential accelerated approval and post-approval requirements, priority review of an investigational new drug application, and other opportunities to expedite development and review.

“We are delighted to receive FDA RMAT designation for both candidates in our heme program designed to treat patients with AML, ALL, and MDS undergoing allogeneic HCT with reduced intensity conditioning, based on encouraging initial data from the ALLOHA trial,” said Chrystal U. Louis, MD, chief medical officer, in a press release. “This is an important milestone that recognizes the transformative potential of our engineered TCR-T therapy candidates, TSC-100 and TSC-101, in multiple difficult-to-treat cancers. We look forward to working closely with the FDA in our ongoing commitment to deliver life-changing therapies to patients.”

Hematology: © immimagery - stock.adobe.com

TSC-100 and TSC-101 each target minor histocompatibility antigens HA-1 and HA-2, respectively, and work to eliminate all recipient hematopoietic cells. This includes malignant, pre-malignant, and normal cells that persist post-transplant. At the same time, they leave donor-derived cells unaffected.

This RMAT for TSC-100 and TSC-101 is supported by initial data from the ALLOHA trial. TScan Therapeutics, the company developing the treatments, noted in the press release that it had provided an update on its phase 1 hematologic malignancies program on May 13, 2024, which included follow-up on all 8 patients being treated with TSC-100 or TSC-101 on the study and 2 patients receiving the control.

At a median follow-up of over 10 months, all 8 patients in the treatment arm were still relapse-free and did not have signs of detectable disease. Further, there were no dose-limiting toxicities observed.

In the control arm, 2 of 8 patients relapsed about 6 months after undergoing transplant. One of the 2 patients died approximately 3 months later. A third patient in the control arm of the trial needed clinical intervention due to concerns regarding impending relapse, and another died post-transplant.

ALLOHA is a multicenter, non-randomized, concurrent controlled, interventional, open-label, phase 1 study where investigators are evaluating the safety, feasibility, and preliminary efficacy of TSC-100 and TSC-101 given at an escalating dose regimen of up to 2 doses for the treatment of patients with AML, MDS, or ALL following HCT from a haploidentical donor.²

In the first arm, TSC-100 plus standard-of-care (SOC) treatment will be given to HA-1–positive patients. The second arm will evaluate TSC-101 plus SOC in HA-1–negative and HA-2–positive patients. The final arm will be the control group who will be treated with just the SOC.

Male and female patients aged ≥ 18 years are eligible for enrollment in the study if they have an ECOG performance status of 0, 1, or 2, are preparing to undergo allogeneic HCT for AML, ALL, or MDS, and more. Patients, both male and female, also must consistently use contraception.

The primary end points include the occurrence of dose-limiting toxicities and adverse events. Secondary end points of the trial are disease-free survival, relapse rates, and overall survival.

The study is actively recruiting patients and has an estimated completion date of June 2025.

REFERENCES:

1. TScan Therapeutics receives FDA’s regenerative medicine advanced therapy (RMAT) designation for its two lead TCR-T therapy candidates for the treatment of heme malignancies. News release. TScan Therapeutics, Inc. May 29, 2024. Accessed May 30, 2024. https://tinyurl.com/mujnteb2

2. A study of TSC-100 and TSC-101 in AML, ALL and MDS patients undergoing haploidentical donor transplantation. ClinicalTrials.gov. Updated February 6, 2024. Accessed May 30, 2024. https://clinicaltrials.gov/study/NCT05473910?term=TSCAN&checkSpell=false&rank=5