Dr Juneko Grilley-Olson Discusses New Findings, Future Directions for Alliance A091902 Trial in Angiosarcoma

In the Rapid Oral Abstracts Session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO), new data from the Alliance A091902 trial were presented on the role of immunotherapy in soft tissue sarcoma treatment.¹ This phase 2 trial is currently investigating paclitaxel with and without nivolumab in patients who are taxane naive and nivolumab plus cabozantinib in taxane-pretreated patients.²

Juneko Grilley-Olson, MD, associate professor of medicine, Duke University School of Medicine, and member, Duke Cancer Institute, presented these most recent findings in the abstract “Alliance A091902: A Multicenter Randomized Phase II Trial of Paclitaxel (P) With and Without Nivolumab (N) in Patients (pts) With Advanced Angiosarcoma (AS).”

“This trial, at times, was the fastest accruing trial within the Alliance Network,” Grilley-Olson says. “And with a rare cancer, it shows that patients are there, we can get the trial done, and it's not something that shouldn't be studied just because it's a rare cancer.”

Transcript

Can you discuss the ongoing Alliance A091902 study findings?

The Alliance A91902 was a study that had 2 main portions. Last year, we presented the data for cabozantinib and nivolumab in patients with taxane-pretreated angiosarcomas. This was a single-arm phase 2 study with an overall response rate of 59%, which is tremendously higher than we've seen in prior angiosarcoma studies. So that was a very exciting outcome. That portion had completed and been reported out last year.³

This year, we presented the randomized portion in patients that are taxane naive. Patients were randomized to receive paclitaxel plus or minus nivolumab. In this portion, the primary outcome was progression-free survival in an unselected angiosarcoma patient population. Everyone could not have received prior taxanes but could have received other lines of therapy. So, a small number received doxorubicin-based or anthracycline-based prior chemotherapies. Most in this cohort had locally advanced or metastatic angiosarcomas.

We saw progression-free survival of 8 months in the paclitaxel monotherapy arm, which outperformed any historic controls. And so the study did not meet its primary end point of an improvement of 3 months from paclitaxel to the combination, with a trend toward benefit in the scalp-face subpopulation—but there we saw a doubling of overall survival from 8.3 to 16 months. It was not powered to detect a significant difference, but it was a suggestion of benefit in that particular population.

We're still looking at the data, trying to understand the implications of this negative outcome and where to go from here.

What are your next steps for this investigation?

We're certainly thinking about the next steps. The most compelling data were the data presented at ASCO 2023, with cabozantinib and nivolumab—so we're thinking more about a platform somewhat more analogous to that, really, as the most promising data that had a progression-free survival of over 9 months. The question is, where to go from here with that. Probably moving that to be randomized in combination vs some kind of standard-of-care chemotherapy.

The other parts that was really a credit to the sarcoma community and the patients as a whole was really the rapid rate that this trial accrued. This trial, at times, was the fastest-accruing trial within the Alliance Network. And with a rare cancer, it shows that patients are there, we can get the trial done, and it's not something that shouldn't be studied just because it's a rare cancer.

References

1. Grilley-Olson JE, Allred JB, Schuetze S, et al. Alliance A091902: A multicenter randomized phase II trial of paclitaxel (P) with and without nivolumab (N) in patients (pts) with advanced angiosarcoma (AS). Presented at: ASCO 2024; May 31-June 4, 2024; Chicago, IL. Abstract 11514. https://meetings.asco.org/2024-asco-annual-meeting/15798?presentation=231578#231578

2. Testing the addition of nivolumab to chemotherapy in treatment of soft tissue sarcoma. ClinicalTrials.gov. Updated May 17, 2024. Accessed June 4, 2024. https://clinicaltrials.gov/study/NCT04339738

3. Grilley-Olson JE, Allred JB, Davis EJ, et al. A multicenter phase II study of cabozantinib + nivolumab for patients (pts) with advanced angiosarcoma (AS) previously treated with a taxane (Alliance A091902). J Clin Oncol. 2023;41(s16). doi:10.1200/JCO.2023.41.16_suppl.115