Dr Wilky on a Study of Botensilimab Plus Balstilimab in Refractory Metastatic Sarcoma

Breelyn Wilky, director, Sarcoma Medical Oncology, The Cheryl Bennett and McNeilly Family Endowed Chair in Sarcoma Research, deputy associate director, Clinical Research, associate professor, medicine, medical oncology, the University of Colorado Medicine, discusses updated findings from a phase 1 study (NCT03860272) investigating the combination of botensilimab (AGEN1181) and balstilimab (AGEN2034) in patients with refractory metastatic sarcoma.

Treatment with botensilimab plus balstilimab produced notable efficacy results across all patients with sarcoma enrolled in the trial, Wilky says. Among 52 response-evaluable patients, the overall response rate (ORR) was 23% (95% CI, 13%-37%), including best overall responses of complete response (CR; 2%), partial response (PR; 21%), stable disease (SD; 44%), and progressive disease (PD; 33%). The median duration of response (DOR) in the overall population was 21.7 months (95% CI, 3.4-not reached [NR]), and the clinical benefit rate (CBR) at 24 weeks was 35% (95% CI, 22%-49%).

Furthermore, among 18 evaluable patients with angiosarcoma, the ORR was 39% (95% CI, 17%-64%), including best overall responses of CR (6%), PR (33%), SD (44%), and PD (17%). The median DOR was 21.7 months (95% CI, 1.9-NR), and the CBR at 24 weeks was 44% (95% CI, 22%-69%). Responses were seen in the angiosarcoma cohort among patients with cutaneous angiosarcoma, an immune-hot subtype, as well as visceral angiosarcoma, she emphasizes. Among patients with visceral angiosarcoma, (n = 9) the ORR was 44%. Among patients with cutaneous angiosarcoma (n = 9), the ORR was 33%.

In the overall population, at a median follow-up of 9.1 months (range, 1.4-39.7), the median overall survival (OS) was NR (95% CI, 14.0 months-NR), and the 12-month OS rate was 69% (95% CI, 52%-81%). In the population of patients with angiosarcoma, at a median follow-up of 6.9 months (range, 1.4-39.7), the median OS was NR (95% CI, 5.0 months-NR), and the 12-month OS rate was 64% (95% CI, 1.4%-39.7%).

Dr Wilky reports having consulting or advisory roles with Aadi Bioscience, Boehringer Ingelheim, Deciphera, Epizyme, and SpringWorks; receiving research funding from Exelixis; and receiving travel, accommodations, or expenses support from Agenus Inc.

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Breelyn Wilky, MD, discusses updated findings from a phase 1 study investigating botensilimab plus balstilimab in refractory metastatic sarcoma.

Breelyn Wilky, MD, an associate professor of Medicine, Sylvester Comprehensive Cancer Care, University of Miami Health System, discusses how to determine which treatment a patient with sarcoma should receive.

The pathology and biology are important when determining how to treat a patient with sarcoma, explains Wilky.

There are some patients who may be candidates for chemotherapy, whereas others might not be able to tolerate such a significant treatment, states Wilky. In the future, genetic information and further immune-profiling information will help to customize treatments further.

Dr. Wilky on Determining Treatments for Sarcoma

Breelyn Wilky, MD, an associate professor of Medicine, Sylvester Comprehensive Cancer Care, University of Miami Health System, discusses the design of a phase II trial investigating concurrent axitinib (Inlyta) and pembrolizumab (Keytruda) in patients with advanced alveolar soft part sarcoma and other soft tissue sarcomas. 

Immunotherapy has dramatic responses for patients with sarcoma but it doesn’t work for everyone, states Wilky. One of the reasons oncologists believe immunotherapy may not be as successful is the potential problem of getting the immune cells into the tumor. The immune cells must be in the right location for them to be activated by the checkpoint inhibitors. 

Research has been done to demonstrate that VEGF also has direct effects in shutting down the immune system in tumors. The concept of this phase II trial was to use a VEGF blocker to allow immune cells into the tumor and then use the checkpoint inhibitor.

Breelyn Wilky, MD, an associate professor of Medicine, Sylvester Comprehensive Cancer Care, University of Miami Health System, discusses the design of a phase II trial investigating concurrent axitinib (Inlyta) and pembrolizumab (Keytruda) in patients with advanced alveolar soft part sarcoma and other soft tissue sarcomas.

Dr. Wilky on Immunotherapy Trial in Sarcoma

Breelyn Wilky, MD, an associate professor of Medicine, Sylvester Comprehensive Cancer Care, University of Miami Health System, discusses the status of a phase II trial investigating concurrent axitinib (Inlyta) and pembrolizumab (Keytruda) in patients with advanced alveolar soft part sarcoma and other soft tissue sarcomas.

This is a clinical trial that is currently in progress, Wilky explains. Therefore, there are not yet any published findings. However, she adds, there are 13 of the 30 planned patients enrolled, several of which have alveolar soft part sarcoma, but also other histologies in soft tissue sarcoma.

She explains that there have not been any prohibitive, severe toxicities from the combination. It is hopeful that preliminary results will be ready to be presented at the 2017 ASCO Annual Meeting.

Dr. Wilky on Ongoing Trial of Pembrolizumab and Axitinib in Sarcoma

Breelyn Wilky, MD, an associate professor of Medicine, Sylvester Comprehensive Cancer Care, University of Miami Health System, discusses a phase II trial exploring concurrent axitinib (Inlyta) and pembrolizumab (Keytruda) in advanced alveolar soft part sarcoma and other soft tissue sarcomas.

This study is designed to carry immunotherapy one step further, Wilky explains. Although immunotherapy has been found to have some dramatic responses in the field, it does not work for all patients. One of the reasons for the lack of efficacy, she adds, may be due to challenges getting the immune cells into the tumor.

Researchers have shown that the VEGF protein, which most people believe as being responsible for forming new blood vessels to feed tumors, also has direct effects on shutting down the immune system in tumors. Therefore, the concept of the phase II trial, she adds, is to use a VEGF blocker to prime the tumor microenvironment and get immune cells into the tumor. Then, the checkpoint inhibitor pembrolizumab can be used to turn them on.

Breelyn Wilky, MD

Articles

Dr Wilky on a Study of Botensilimab Plus Balstilimab in Refractory Metastatic Sarcoma

Dr. Wilky on Determining Treatments for Sarcoma

Dr. Wilky on Immunotherapy Trial in Sarcoma

Dr. Wilky on Ongoing Trial of Pembrolizumab and Axitinib in Sarcoma

Dr. Wilky on Pembrolizumab Plus Axitinib in Sarcoma