TCR² Announces RECIST Response in Ovarian Cancer from Ongoing Phase 1/2 Trial of TC-210 in Treatment Refractory Mesothelin-Expressing Solid Tumors

Rhea-AI Summary

TCR² Therapeutics (TCRR) reported promising interim results from its Phase 1 trial of TC-210 (gavo-cel) for mesothelin-expressing solid tumors. All eight patients showed tumor regression, with a 50% overall response rate, including a confirmed partial response in one ovarian cancer patient. Safety remains manageable, with few adverse effects reported. The trial design was amended to accelerate treatment, reducing safety observation periods. A conference call to discuss these results is scheduled for December 14, 2020.

Positive

• 50% overall response rate among patients infused with TC-210.
• Tumor regression observed in all first eight patients treated.
• Single-agent gavo-cel displayed efficacy in an ovarian cancer patient.
• Manageable toxicity profile with no neurotoxicity reported.
• Trial design amended to accelerate treatment timelines.

Negative

• None.

- TC-210 induced tumor regression in all of the first eight patients

- Ovarian cancer patient achieved confirmed RECIST partial response (PR)

- Overall response rate (ORR) 50% in patients infused with TC-210 and lymphodepletion

      - Continued manageable toxicity profile

      - Phase 1 trial amended to accelerate treatment

- TCR² to host conference call Monday, December 14 starting at 8:00am E.T. live webcast available

CAMBRIDGE, Mass., Dec. 13, 2020 (GLOBE NEWSWIRE) -- TCR² Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company with a pipeline of novel T cell therapies for patients suffering from cancer, today announced positive interim data from the ongoing Phase 1 portion of the TC-210 ( gavocabtagene autoleucel or “gavo-cel”) Phase 1/2 clinical trial for mesothelin-expressing solid tumors. As of the November 24, 2020 data cutoff, three PRs according to RECIST 1.1 criteria have been recorded among the first eight patients treated on study, with our first ovarian cancer patient having achieved a confirmed PR up to month six. In addition, the first patient treated at a higher gavo-cel dose (1x10⁸/m²) without lymphodepletion achieved stable disease through two months without any significant toxicities, which has allowed patients to start treatment at that dose with the addition of lymphodepletion. The toxicity profile remains manageable with only two patients to date exhibiting gavo-cel-related non-hematologic grade >2 toxicity and no evidence of neurotoxicity or on-target, off-tumor toxicity. Translational data further demonstrated TRuC-T cell expansion and cytokine induction in all patients.

“Although the focus of any Phase 1 trial is safety, the consistency in tumor regression and RECIST responses we have observed with gavo-cel as a single agent supports our belief in the advantages of TRuC-T cells over other cell therapies and the potential for a fundamentally new approach in the treatment of solid tumors,” said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR² Therapeutics. “The HLA independence of our technology allows us to treat a broad population of patients with mesothelin surface expression while leveraging the full T cell receptor complex to drive enhanced trafficking, on-target killing and persistence in the hostile solid tumor microenvironment. Most important, we are delivering clinical and survival benefit to those patients with heavily pre-treated mesothelioma or ovarian cancer.”   

“The ability of gavo-cel to benefit patients who have become treatment refractory after having failed multiple lines of therapy, including immune checkpoint inhibitors and anti-mesothelin therapy, combined with its manageable safety profile is remarkable. The changes announced today to the Phase 1 trial design, reducing the intra-cohort safety observation periods to 14 days from 28 days, enable us to more rapidly identify the recommended Phase 2 dose and initiate the Phase 2 expansion trial where we will evaluate the efficacy of gavo-cel in four solid tumor indications. Importantly, in the Phase 2 we will explore the impact of gavo-cel retreatment and its combination with checkpoint inhibitor therapy which could further improve on the clinical benefit observed to date,” said Alfonso Quintás-Cardama, M.D., Chief Medical Officer of TCR² Therapeutics.

The primary objectives of the Phase 1 portion of the study are to define the safety profile of gavo-cel in patients whose tumors overexpress mesothelin and to determine the recommended Phase 2 dose (RP2D). Secondary objectives include ORR and disease control rate (DCR). Exploratory objectives include the assessment of expansion, tumor infiltration, and persistence of gavo-cel.

Summary of trial conduct, baseline characteristics and gavo-cel dose:

• Safety Protocol: The new clinical trial protocol amendment allows the intra-cohort safety observation periods to be reduced to 14 days from 28 days, allowing the testing of a gavo-cel dose over a minimum of 56 days compared to the previous 84 days.
• Screening:   Forty-five percent of patients met the mesothelin expression cut-off as defined per protocol.
• Manufacturing: Products meeting protocol defined specifications for gavo-cel have been manufactured successfully for each patient from whom apheresis material was sent into production.
• Patient Characteristics: Eight patients received gavo-cel including seven with mesothelioma and one with ovarian cancer with a median age of 65 years (range, 36-84 years). The median number of prior therapies was 5.5 (range, 3-9), including immune checkpoint inhibitor therapy (n=6) and anti-mesothelin therapies (n=3).
• Gavo-cel Dose: The eight patients disclosed to date have received gavo-cel at the following dose level (DL):
  • DL 0: 5x10⁷ cells/m² without lymphodepletion – 1 mesothelioma
  • DL 1: 5x10⁷ cells/m² following lymphodepletion – 5 mesothelioma and 1 ovarian cancer
  • DL 2: 1x10⁸ cells/m² without lymphodepletion – 1 mesothelioma

Key clinical findings from the first eight patients treated with gavo-cel:

• Safety: Gavo-cel was generally well tolerated, with no patients experiencing neurotoxicity or on-target, off-tumor toxicities. Two (25%) patients experienced Cytokine Release Syndrome (CRS) grade 3, which was successfully managed with tocilizumab and corticosteroids.
• Clinical Activity: All eight pat

FAQ

What were the results of TCRR's Phase 1 trial for TC-210?

The Phase 1 trial for TC-210 showed a 50% overall response rate with tumor regression in all first eight patients treated.

What is the safety profile of TC-210 according to the recent TCRR press release?

TC-210 has a manageable safety profile, with no neurotoxicity reported and only two patients experiencing serious cytokine release syndrome.

What changes were made to the Phase 1 trial design of TCRR?

The trial design was amended to reduce intra-cohort safety observation periods from 28 days to 14 days, allowing quicker patient assessment.

When will TCRR discuss the interim results of TC-210?

TCRR will host a conference call on December 14, 2020, to discuss the interim results of the TC-210 trial.