Botensilimab Plus Balstilimab Elicits Durable Responses in Refractory Metastatic Sarcoma

Treatment with the combination of botensilimab (AGEN1181) and balstilimab (AGEN2034) elicited deep and durable responses in the extended survival of patients with refractory metastatic sarcoma, according to findings from a phase 1 study (NCT03860272) presented at the 2024 ESMO Congress.

Most notably, responses were observed in patients with angiosarcoma, which has historically been a more difficult-to-treat subgroup, according to lead study author Breelyn Wilky, MD.

Findings showed that efficacy-evaluable patients with refractory metastatic sarcoma (n = 52) achieved an overall response rate (ORR) of 23% (95% CI, 13%-37%), which comprised a 2% complete response rate, a 21% partial response rate, a 44% stable disease rate, and a 33% progressive disease rate. Additionally, the median duration of response (DOR) 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%).

In the subgroup of patients with angiosarcoma (n = 18), the ORR was 39% (95% CI, 17%-64%), including an ORR of 33% for patients with cutaneous angiosarcoma (n = 9) and an ORR of 44% in patients with visceral angiosarcoma (n = 9). The median DOR for this subgroup was 21.7 months (95% CI, 1.9-NR), and the 24-week CBR was 44% (95% CI, 22%-69%).

“We are continuing to enroll [patients] to this phase 1 expansion cohort for sarcoma; a phase 2 clinical trial is also under consideration,” Breelyn Wilky, MD, said in an interview with OncLive^®.

In the interview, Wilky shared insights on the updated efficacy findings with the combination of botensilimab plus balstilimab in patients with refractory metastatic sarcoma. She also detailed the potential implications of these findings and the next steps for this research.

Wilky serves as director of Sarcoma Medical Oncology, The Cheryl Bennett and McNeilly Family Endowed Chair in Sarcoma Research, deputy associate director of Clinical Research, and an associate professor of medicine in Medical Oncology at University of Colorado Medicine in Aurora.

OncLive: What was the primary goal of the C-800-01 trial?

Wilky: The C-800-01 phase 1 trial of botensilimab plus balstilimab is a huge study that's enrolled nearly 500 patients with advanced solid tumors across the board. Because of the impressive [disease] control and activity that they saw across that trial, investigators established multiple expansion cohorts, one of which was for patients with sarcoma. At the 2024 ESMO Congress, I reported on the updated results for efficacy and safety for the sarcoma cohort.

What findings have been previously reported from the sarcoma cohort of this study?

We presented early data [in 2023] for the sarcoma cohort, both at the ESMO Congress and then at the Connective Tissue Oncology Society Annual Meeting. We had seen some promising signals of activity. Since that time, we've had longer follow-up for those patients, and we enrolled additional patients with angiosarcoma, which is a particularly problematic type of sarcoma; particularly, the visceral subtypes tend not to respond to immunotherapy.

The data that I presented [at the 2024 ESMO Congress] were the updated, longer-term follow-up. Excitingly, we're seeing some impressive results in the angiosarcoma cohort with those newly enrolled patients.

What efficacy data were shared at the 2024 ESMO Congress?

Overall, we're excited to continue to see impressive results across the whole sarcoma cohort. Of 52 patients who were evaluable for response, we saw an ORR of 23%. However, the duration of those responses was impressive with a median DOR of 21.7 months; many of those responses have gone on to be durable.

What I'm most excited about is in the group of 18 evaluable patients with angiosarcoma, the ORR was 39%, and [responses were observed in] not just in the immune, hot, cutaneous angiosarcoma subtypes, but also in visceral angiosarcomas. If we only look at that group, the visceral angiosarcoma ORR was 44%, which is incredible.

What updated safety data were reported?

The safety profile hasn't changed much. We didn't see much difference in the sarcoma cohort compared with the overall safety profile. There were no new safety signals that emerged, no unexpected immune signals outside of the class, and there were no grade 4/5 treatment-related adverse effects.

The most common immune-related toxicity continued to be colitis and diarrhea, which was manageable and reversible with steroids and TNF-α–blocking therapies.

What are the potential implications of these findings?

In general, immune checkpoint inhibitors in sarcoma have a few signals of activity, but typically [that activity is seen] only in a few subtypes: the immune-hot sarcoma subtypes. What we're seeing from the updated data presented [from C-800-01] is that we’re seeing activity in visceral angiosarcomas, leiomyosarcomas, and dedifferentiated liposarcomas, which are immune-cold, difficult-to-treat sarcoma subtypes.

My personal hope is that botensilimab winds up being the immune checkpoint inhibitor of choice when we’re looking at sarcomas, not just for the immune-hot subtypes, but also for subtypes that are traditionally harder to treat.

[Furthermore], sarcomas are not the only immune-cold tumor where botensilimab has shown activity]. It's designed to extend the reach of immunotherapy to immune-cold tumors across the board. In the sarcoma world, we're excited to be a part of that and to see those benefits translate to our patients.

Disclosures: Dr Wilky reported serving in a consulting or advisory role for Aadi Bioscience, Adcendo, Boehringer Ingelheim, Deciphera, Epizyme, Polaris, and SpringWorks; receiving research funding from Exelixis; and receiving travel, accommodations, or expenses support from Agenus.

Reference

Wilky BA, Trent JC, Tsimberidou AM, et al. Updated efficacy and safety of botensilimab plus balstilimab in patients with refractory metastatic sarcoma from an expanded phase 1 study. Ann Oncol. 2024;35(suppl 2):S1034. doi:10.1016/j.annonc.2024.08.1818.