Immune-agonist combo has activity against several tumor types

June 5, 2017|Breast Cancer ICYMI

AT ASCO 2017

For example, a 44-year-old woman with metastatic cervical cancer – a tumor type known to have high levels of GITR expression – had received more than three prior lines of therapy, including chemotherapy with a vascular endothelial growth factor inhibitor. She had a partial response with the combination, with an approximately 62% reduction in tumor burden. She had an ongoing response to the combination at the time of data cutoff in March 2017.

The combination also showed efficacy against adenocarcinoma of the hepatopancreatic duct (ampulla of Vater), a tumor type not typically responsive to immunotherapy. The 60-year-old patient (sex not disclosed), had received three prior lines of chemotherapy and also had a partial response at the 240/240 dose, with the best change in tumor burden an estimated 38% reduction. The duration of the response at the time of data cutoff was 16 weeks and was ongoing.

Two other patients had partial responses after progression on an anti-PD-1 agents, including one with nasopharyngeal cancer who had received three prior lines of therapy, including chemotherapy and a PD-1 inhibitor. This patient had an approximately 43% reduction in tumor burden, with a 17-week duration of response and ongoing response at data cutoff.

The other patient was a 59-year-old with malignant melanoma that had advanced on pembrolizumab (Keytruda). This patient too had received three prior lines of therapy, including a BRAF inhibitor, anti-PD-1, and BRAF/MEK inhibitor combination.

This patient had a response of 24-week duration at the time of data cutoff. It is ongoing, Dr. Liu said.

“This combination of immune agonists was safe with a low incidence of severe toxicity, and there was no maximum tolerated dose; however, the maximum administered dose may not be the most effective dose to move forward,” commented Siwen Hu-Lieskovan MD, PhD, from the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, the invited discussant.

She noted that activity of the combination has been seen in a wide range of tumor histologies but added that further biomarker studies will be critical for identifying patients who are likely to respond.

The study was funded by Bristol-Myers Squibb. Dr. Siu disclosed research funding from the company and others and consulting/advising several different companies. Dr. Hu-Lieskovan disclosed institutional research funding from BMS and other companies, as well as honoraria and consulting and serving in an advisory capacity for companies other than BMS. Several coauthors are employees of the company.