TCR2 Therapeutics Announcement
TCR2 Therapeutics (TCRR) – a clinical-stage immunotherapy company with a pipeline of novel T cell therapies for cancer, announced positive interim data from the first five patients treated in the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for mesothelin-expressing solid tumors. All five patients have demonstrated tumor regression including two RECIST unconfirmed partial responses (one of which remains subject to independent central review) and two patients with stable disease through six months.
The toxicity profile has been manageable and was observed only in one patient exhibiting TC-210-related non-hematologic grade >2 toxicity but no evidence of neurotoxicity or on-target, off-tumor toxicity.
The TCR2 Officers Had This to Say
Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics, said, “We are delighted that our very first dose of TC-210 induced consistent tumor regression and clinical benefit in heavily pre-treated cancer patients. There are very few options for patients with solid tumors and those expressing mesothelin represent a significant frontier of unmet medical needs. While these are early data requiring further study, we are encouraged by the potential of our TRuC-T cells as we continue to enroll and treat patients with the goal of quickly finding a recommended Phase 2 dose for TC-210.”
Alfonso Quintás-Cardama, M.D., Chief Medical Officer of TCR2 Therapeutics, said, “Based on my prior experience working with both TCR-T and CAR-T cells, including the FDA approval of Kymriah, observing consistent clinical benefit in patients at presumably suboptimal T cell doses is quite meaningful. These early TC-210 data suggest our approach may overcome the challenges faced by many T cell therapies in the hostile solid tumor microenvironment. Our enrolled patients have failed multiple lines of therapy, including standard chemotherapy, checkpoint inhibitors and in some cases other mesothelin-directed approaches, in indications where survival has been historically shorter than six months.”
About the Phase 1/2 Clinical Trial in Advanced Mesothelin-Expressing Solid Tumors
- The Phase 1/2 clinical trial (NCT03907852) is evaluating the safety and efficacy of TC-210 – TCR2’s T-cell receptor fusion construct directed against mesothelin. The trial is enrolling patients with mesothelin expressing NSCLC, ovarian cancer, cholangiocarcinoma and malignant pleural/peritoneal mesothelioma.
- The Phase 1 dose escalation portion of the clinical trial utilizes a modified 3+3 design with four increasing TC-210 T cell doses. At each dose TC-210 will be tested in two separate dose levels: first without lymphodepletion and then following lymphodepleting chemotherapy.
- The Phase 1 portion of the clinical trial is ongoing.
Trial Objectives and Findings
- The primary objectives: Defining the safety profile of TC-210 in patients whose tumors overexpress mesothelin and to determine the recommended Phase 2 dose (RP2D).
- The secondary objectives: Overall response rate (ORR) and disease control rate (DCR). Exploratory objectives include the assessment of expansion, tumor infiltration, and persistence of TC-210 T cells.
Summary of Trial Conduct, Baseline Characteristics and TC-210 Dose:
- Screening: Forty-eight percent of patients met the mesothelin expression cut-off as defined per protocol.
- Manufacturing: TC-210 T cell products have been manufactured successfully for each patient enrolled in the clinical trial.
- Patient Characteristics: TC-210 treated patients included four with mesothelioma and one with ovarian cancer with a median age of 61 years (range, 36-74 years). The median number of prior therapies was five (range, 3-9), including immune checkpoint inhibitor therapy and the anti-mesothelin ADC anetumab ravtansine.
Key Clinical Findings from the First Five Patients Treated with TRuC-T Cells Include:
- Safety: TC-210 was generally well tolerated. No experienced neurotoxicity or on-target, off-tumor toxicities. Three (60%) patients experienced Cytokine Release Syndrome (CRS), which was Grade 1 in two patients and Grade 3 in one patient. The patient experiencing Grade 3 CRS also developed Grade 3 pneumonitis during the first-week post-infusion that responded to tocilizumab and steroid therapy. This patient died 34 days post-treatment due to fungal sepsis, which was deemed unrelated to TC-210. Because of the earlier pneumonitis event, the Safety Review Team recommended the expansion of the cohort from three to six patients. None of the subsequent three patients treated at DL1 developed pneumonitis or CRS above Grade 1.
- Clinical Activity: All five patients treated with TC-210 T cells have had at least one disease response assessment. The disease control rate (DCR) was 100%, with all patients experiencing tumor regression. The overall response rate (ORR) was 40% (2 unconfirmed PRs) according to RECIST v1.1. The TC-210 therapy induced a significant reduction in F-fluorodeoxyglucose (FDG) by PET imaging in two evaluable patients, including one patient who achieved a complete metabolic response (PR by RECIST v1.1).
What is Mesothelin?
Mesothelin: a cell-surface glycoprotein highly expressed in a wide range of solid tumors, including malignant pleural/peritoneal mesothelioma, ovarian cancer, cholangiocarcinoma, breast cancer, pancreatic cancer and others.
It is important to note that overexpression of mesothelin is associated with poorer prognosis.
Solid tumors expressing mesothelin: Non-small cell lung cancer, ovarian cancer, mesothelioma and cholangiocarcinoma represent a significant patient population up to 80,000 in the United States alone.
Conference Call and Webcast
TCR2 Therapeutics hosted a conference call and webcast today, July 27th, at 8:00 am E.S.T. A replay will be available on the Company’s website for approximately 30 days.
About TCR2 Therapeutics
TCR2 Therapeutics Inc. is a clinical-stage immunotherapy company developing a pipeline of novel T cell therapies for solid tumors or hematological malignancies.
TCR2’s proprietary T cell receptor (TCR) Fusion Construct T cells (TRuC®-T cells) specifically recognize and kill cancer cells by harnessing signaling from the entire TCR, independent of human leukocyte antigens (HLA). In preclinical studies TRuC-T cells demonstrated superior anti-tumor activity compared to chimeric antigen receptor T cells (CAR-T cells) while secreting lower levels of cytokine release.
The Company’s lead TRuC-T cell product candidate targeting hematological malignancies, TC-110, is currently being studied in a Phase 1/2 clinical trial to treat patients with CD19-positive adult acute lymphoblastic leukemia (aALL) and with aggressive or indolent non-Hodgkin lymphoma (NHL). For more information about TCR2, please visit www.tcr2.com.
|Stock Price||$16.15 UP $3.05|
|Market Cap.||$388.83 million|
Although it is early clinical trial news, it has encouraging results so we will keep our eyes on this firm’s activities and future clinical trial results.
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