Early Data Show Clinical Benefit With Gavocabtagene Autoleucel in Advanced Solid Tumors

The anti-mesothelin cell therapy gavocabtagene autoleucel (gavo-cel) tolerably improved clinical outcomes in patients with advanced mesothelin-expressing solid tumors, according to data from the phase 1 portion of a clinical trial laid out in a recent press release from TCR² Therapeutics.

These data come from an ongoing phase 1/2 trial (NCT03907852) of gavo-cel in patients with malignant pleural/peritoneal mesothelioma (MPM), non–small cell lung cancer (NSCLC), ovarian cancer, or cholangiocarcinoma. Treatment with gavo-cel led to a disease control rate, defined as a response or sustained stable disease for at least 3 months post-infusion, of 77% across 30 evaluable patients with MPM, ovarian cancer, or cholangiocarcinoma. Tumor regression (range, 4%-80%) occurred in 93% of patients as measured by blinded independent central review (BICR). Target lesion regression greater than 30% occurred in 8 patients, of whom 6—4 with mesothelioma and 2 with ovarian—achieved a partial response according to RECIST v1.1 criteria. Moreover, the overall response rate (ORR) by BICR was 29% and 21%, respectively, among patients with ovarian cancer and MPM. The median progression-free survival (PFS) was 5.8 months and median overall survival (OS) was 8.1 months among patients with ovarian cancer, and 5.6 months and 11.2 months, respectively, among patients with MPM.

“The results of the phase 1 trial underscore the potential clinical value of gavo-cel in a very heavily pretreated patient population that are receiving our engineered T cells as their sixth line of therapy on average,” Alfonso Quintás-Cardama, MD, chief medical officer of TCR² Therapeutics, said in a press release. “These results clearly support the further development of gavo-cel in the phase 2 portion of the study where we believe that the combination with checkpoint inhibitors and the ability to retreat patients with additional doses of gavo-cel will allow us to increase patients’ exposure to gavo-cel, potentially translating into even higher response rates and improved durability of benefit.”

Gavo-cel is a T-cell receptor fusion construct directed against the cell-surface glycoprotein mesothelin, overexpression of which is associated with poorer prognoses in some solid tumors, including ovarian cancer, MPM, and cholangiocarcinoma.

The phase 1 portion of this trial evaluated 30 patients who received 4 escalating doses of gavo-cel as part of a modified 3+3 design. The treatment was tested in 2 separate dose levels at each escalating dose: first without lymphodepletion and then following lymphodepletion. In the upcoming phase 2 portion of this trial, 75 patients in an MPM cohort and 20 patients each in ovarian, NSCLC, and cholangiocarcinoma cohorts will receive gavo-cel at the recommended phase 2 dose of 1 × 108 cells/m² following lymphodepletion.

Patients were required to have pathologically confirmed MPM, NSCLC, serious ovarian adenocarcinoma, or cholangiocarcinoma at screening to be included in this trial. Patients must also have received between 1 and 5 prior systemic standard-of-care therapies for metastatic or unresectable disease. Adequate organ function as indicated by the laboratory values in the clinical protocol and an ECOG performance status not greater than 1 were among the other inclusion criteria.

Reference

Gavo-cel Continues to Demonstrate Clinical Benefit in Solid Tumors with Additional RECIST Reponses in Ovarian Cancer and Mesothelioma. News Release. TCR² Therapeutics. September 28, 2022. Accessed September 29, 2022. https://bit.ly/3y6jYQv