Gavo-Cel to Be Evaluated With Nivolumab, Ipilimumab for Solid Tumors

TCR² Therapeutics is collaborating with Bristol Myers Squibb to evaluate their gene therapy, gavo-cel, in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) in a planned phase 2 clinical trial in treatment refractory mesothelin-expressing solid tumors.¹

“We are very pleased to establish a collaboration agreement with Bristol Myers Squibb for our Phase 2 clinical trial as this enables us to evaluate the potential synergy between gavo-cel and immune checkpoint inhibitors,” said Garry Menzel, PhD, president and chief executive officer, TCR2 Therapeutics, in a statement.¹ 

The phase 2 trial will evaluate the antitumor activity of gavo-cel in patients with unresectable, metastatic or recurrent mesothelin-expressing non-small cell lung cancer (NSCLC), ovarian cancer, malignant pleural/peritoneal mesothelioma (MPM) and cholangiocarcinoma. The trial will evaluate the selected recommended Phase 2 dose (RP2D) in cohorts according to disease type. Patients with NSCLC, ovarian cancer, or cholangiocarcinoma will receive gavo-cel and nivolumab. Patients with MPM will be treated with gavo-cel alone, gavo-cel and nivolumab, or gavo-cel, nivolumab, and ipilimumab.

“The new standard of care established by Opdivo in difficult-to-treat diseases is important for cancer patients around the world, including the recent approval of the combination of Opdivo and Yervoy as first-line treatment for adult patients with unresectable malignant pleural mesothelioma. We look forward to determining whether gavo-cel can provide additional clinical benefit to these patients,” Menzel added.¹

WATCH NOW: Developing Personalized Immunotherapies for Solid Tumors

TCR2 Therapeutics announced positive data from gavo-cel in refractory mesothelin-expressing solid tumors earlier in October 2021.2 The interim data demonstrated that gavo-cel treatment yielded a disease control rate (DCR) of 81%. 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.

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.

Dose-limiting toxicities included grade 3 pneumonitis, grade 5 bronchoalveolar hemorrhage, and severe cytokine release. The safety review team declared 5 x 10⁸/m² as the maximum tolerated dose following the toxicities. The RP2D is still being refined.

“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.² “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.”

REFERENCES

1. TCR² Therapeutics Announces Clinical Trial Collaboration Agreement with Bristol Myers Squibb to Evaluate Gavo-cel in Combination with Opdivo® and Yervoy® in Mesothelin-Expressing Solid Tumors. News release. TCR2 Therapeutics. October 25, 2021. https://www.biospace.com/article/releases/tcr-therapeutics-announces-clinical-trial-collaboration-agreement-with-bristol-myers-squibb-to-evaluate-gavo-cel-in-combination-with-opdivo-and-yervoy-in-mesothelin-expressing-solid-tumors/
2. 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