49MO - Atezolizumab and bevacizumab in patients treated with prior atezolizumab in alveolar soft tissue sarcoma (ASPS)

Background

Alveolar soft part sarcoma (ASPS) is a rare disease that occurs most frequently in young adult patients (pts). In December 2022, the FDA approved atezolizumab (Atezo) for pediatric and adult patients with metastatic ASPS based on the results of this phase II trial of single-agent Atezo. For study patients who progressed on single-agent Atezo, an anti-VEGF agent, bevacizumab (Bev) was added to potentiate checkpoint inhibitor activity. We are reporting the activity of the combination of Atezo and Bev (Genentech), in pts with advanced ASPS after progression on Atezo.

Methods

Open label, phase II crossover trial; Atezo is administered intravenously at a fixed dose of 1200 mg and Bev at 15mg/kg once every 21 days in adults only. Pts with recent history of hemoptysis are not eligible. The primary objective for this portion of the study is to determine the objective response rate of Atezo plus Bev upon progression with Atezo using RECIST v 1.1. Secondary objectives include duration of response (DOR) and comparison of RECIST v 1.1 vs iRECIST. Biopsies for pharmacodynamic assessment are performed at baseline, prior to cycle 3 day 1, or at any point where there is evidence of clinical response.

Results

Eight pts have crossed over from single agent Atezo as of 1/3/2023. The average age in this group is 24.5 years (17–29). There are 4 female, 2 white, 3 black, 1 Asian, 2 unknown and 1 Hispanic/Latino pts. All 8 pts have the best response of stable disease. Median time on Atezo and Bev is 10.9 months (range, 4.3–19.1) compared to 9.7 months (range, 3.4–40.2) on single-agent Atezo. Six pts are still on treatment; 2 others had progressed post Cycles 5 and 8. Median PFS has not been reached. Grade 3 drug-related adverse events included hypertension (n=1), and lipase increase (n=1). Grade 1/2 seen > 1 pt include hypothyroidism, proteinuria, anemia, nausea, amylase increase, hyponatremia, hypokalemia and headache. No grade 4 or 5 events have been reported.

Conclusions

The combination of Atezo and Bev is well tolerated with no unexpected toxicities. These results are encouraging, and trial is ongoing.

Clinical trial identification

NCT03141684.

Editorial acknowledgement

Legal entity responsible for the study

Alice Chen, M.D., Experimental Therapeutics Clinical Trials Network, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute.

Funding

NIH Contract # 75N91019D00024; Genentech, member of the Roche group, supplied drug and funding.

Disclosure

B.A. Van Tine: Financial Interests, Personal, Invited Speaker, Educational Speaker: Targeted Oncology; Financial Interests, Personal, Advisory Board, Also, Travel paid to conference to present abstract: Adaptimmune Limited; Financial Interests, Personal, Other, Consulting. Also attended and Ad Board meeting. Travel was paid to attend an Ad board meeting: Epizyme; Financial Interests, Personal, Other, Consulting- ADRx working on a cancer project and they are requesting my expertise: ADRx; Financial Interests, Personal, Advisory Board, Tenosynovial Giant Cell Tumors (TGCT): Ayala Pharmaceuticals; Financial Interests, Personal, Other, Consulting and Ad Board: Bayer; Financial Interests, Personal, Other, OncLive Virtual Workshop: Intellisphere Llc; Financial Interests, Personal, Advisory Board, Attended Advisory Board Meeting: Apexigen Inc.; Financial Interests, Personal, Advisory Board, Attended an Advisory Board Meeting: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: PTC Therapeutics, Boehringer Ingelheim, Agenus, Regeneron Pharmaceuticals; Financial Interests, Personal, Other, Consulting: Advenchen; Financial Interests, Personal, Invited Speaker, Sigma-2 Receptor Ligands and Therapeutic uses therefor (006766), Modular Platform for Targeted Therapeutic Delivery (006755), Sigma-2 Receptor Ligand Drug Conjugates as Antitumor Compounds, Methods of synthesis and Uses Thereof (014229): Accuronix Therapeutics; Financial Interests, Institutional, Research Grant: Pfizer, Merck, Tracon Pharm, GSK; Non-Financial Interests, Personal, Invited Speaker, Non-paid: Polaris. All other authors have declared no conflicts of interest.