Gavo-Cel Efficacious in Refractory Mesothelin-Expressing Solid Tumors

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Investigators have identified the maximum tolerated dose and continue to refine the recommended phase 2 dose in the phase 1 part of the study.

TCR2 Therapeutics has announced positive interim data from the phase 1/2 study (NCT03907852) of gavocabtagene autoleucel (gavo-cel; TC-210) for the potential treatment of refractory mesothelin-expressing solid tumors.1

Gavo-cel treatment yielded a disease control rate (DCR) of 81% and investigators observed tumor regression in 15 of 16 evaluable patients. The overall response rate (ORR) was 31%, median overall survival (OS) for patients with mesothelioma is 11.2 months, and median progression free survival (PFS) is 5.9 months.

“The interim gavo-cel data reported today showed continued clinical benefit and a manageable safety profile in a population of patients that previously achieved minimal or no improvement due to the advanced and aggressive state of their cancer,” principal investigator David Hong, MD, deputy chair, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, said in a statement.1 “Patients with treatment refractory cancer have very limited treatment options and will often need hospice and supportive care. We are encouraged by the early survival data from gavo-cel in patients previously treated with checkpoint inhibitors and other therapies.”

As of June 30, 2021, 17 patients, 12 with mesothelioma, 4 with ovarian cancer, and 1 with cholangiocarcinoma, had been dosed with a single gavo-cel infusion as part of the dose escalation portion of the trial. The participants had a median of 5 prior lines of therapy, including immune checkpoint inhibitors (n = 11) and mesothelin-directed therapies (n = 5). Gavo-cel was administered at up to 5 dose levels with and without lymphodepletion, with a highest dose level of 5x108/m2.

READ MORE: Developing Cell Therapies for Solid Tumors and Hematologic Malignancies

Investigators identified 2 dose-limiting toxicities. One case of grade 3 pneumonitis at dose level 1 resolved and dose escalation continued. At dose level 5, 1 case of grade 5 bronchoalveolar hemorrhage occurred and severe cytokine release occurred in all 3 patients at dose level 5. The safety review team declared 5 x 108/m2 as the maximum tolerated dose following the toxicities. Investigators are using a split dosing approach to refine the recommended phase 2 dose, with 1 patient receiving a 3x108/m2 dose. Another patient has been treated at dose level 3. Both patients experienced only grade 1 non-hematological toxicities.

“Our ambition with gavo-cel from the start was to redefine treatment for solid tumors with cell therapies. We are excited to present data demonstrating clinical activity in all three mesothelin-expressing solid tumors treated to date and tumor regression in a majority of patients who are treatment refractory after numerous lines of therapy. We are very encouraged by the progression free survival and overall survival observed among patients with refractory mesothelioma treated so far with gavo-cel in the Phase 1 trial,” Alfonso Quintás-Cardama, MD, chief medical officer, TCR2 Therapeutics, added to the statement.2

Tumor regression was observed in 15 of 16 evaluable patients, with magnitudes ranging from 5% to 75%. A partial response (PR) was achieved in 6 patients, 4 (3 with mesothelioma and 1 with ovarian cancer) according to Response Evaluation Criteria in Solid Tumours 1.1 assessment. Investigators included an additional patient with cholangiocarcinoma as achieving PR for an ORR of 31%, however, independent review kept the ORR at 25%. 

“Based on these data and the most recent patient experiencing a very mild safety profile at a cell dose of 3x108/m2, we believe the identification of the RP2D is close at hand. As we approach the Phase 2 expansion phase, our focus will shift to further optimizing outcomes for patients by studying combinations with immune checkpoint inhibitors, allowing gavo-cel re-treatment and evaluating different mesothelin expression thresholds," Quintás-Cardama added.

Gavo-cel, a T-cell receptor (TCR) fusion construct T cell therapy, was previously granted orphan drug designation by the FDA for the treatment of cholangiocarcinoma in September 2021.

REFERENCES
1. TCR² Therapeutics announces positive interim results from ongoing phase 1/2 trial of gavo-cel for treatment refractory mesothelin-expressing solid tumors. News release. TCR² Therapeutics. September 17, 2021. https://investors.tcr2.com/news-releases/news-release-details/tcr2-therapeutics-announces-positive-interim-results-ongoing
2. TCR² Therapeutics receives FDA orphan drug designation for gavo-cel for the treatment of cholangiocarcinoma. News release. TCR² Therapeutics. September 2, 2021. https://investors.tcr2.com/news-releases/news-release-details/tcr2-therapeutics-receives-fda-orphan-drug-designation-gavo-cel
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