1930P - phase II trial of avelumab in combination with gemcitabine in advanced leiomyosarcoma as a second-line treatment (KCSG UN18-06)

Background

Combined chemotherapy and anti-PD-1/PD-L1 antibody has shown a synergistic antitumor effect in several types of cancers. This study evaluated the efficacy and safety of avelumab plus gemcitabine in patients with leiomyosarcoma (LMS) who failed first-line chemotherapy.

Methods

This is a phase II, multicenter, open-label, single-arm study (NCT03536780). Patients with unresectable, locally advanced, or metastatic LMS received avelumab 10 mg/kg on days 1 and 15 (up to 24 months), plus gemcitabine 1,000 mg/m² on days 1, 8, and 15 of a 28 day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression free-survival (PFS), overall survival (OS), and safety.

Results

Thirty-eight patients were enrolled between October 2018 and May 2022. Responses were observed in 7 out of 35 evaluable patients (ORR, 20%; 95% confidence interval [CI], 8–37%): 1 complete response and 6 partial responses. Disease control rate was 71.4%. Median DOR was 21.0 months (range, 7.6–32.7+ months). With median follow-up of 22.3 months, median PFS was 5.6 months (95% CI, 2.9–8.3 months) and median OS was 24.4 months (95% CI, 18.5–30.3 months). There was no grade 5 adverse event (AE). In safety analysis set (n=37), grade 3–4 AE occurred in 25 (67.6%) patients; neutropenia (n = 19, 51.4%) was the most common. Immune-mediated AEs occurred in 4 (10.8%) patients (hepatitis, n = 2; hypothyroidism, n = 2). There was no significant difference in ORR between PD-L1 -positive (SP263 tumor proportion score ≥1%) and PD-L1 -negative groups (25.0% [3/12] vs. 21.1% [4/19]; P=1.000).

Conclusions

Avelumab plus gemcitabine showed favorable toxicity profiles in patients with LMS. Although the primary endpoint for ORR (35% for P1) was not reached, the DOR, PFS, and OS observed are encouraging. Next-generation sequencing and immune phenotype analyses will be presented.

Clinical trial identification

NCT03536780.

Editorial acknowledgement

Legal entity responsible for the study

Korean Cancer Study Group (KCSG).

Funding

This study was supported by Merck Ltd., Seoul, South Korea, an affiliate of Merck KGaA (CrossRef Funder ID: 10.13039/100009945), as part of an alliance between Merck and Pfizer.

Disclosure

Y.S. Kim: Financial Interests, Institutional, Research Grant: Merck KGaA; Financial Interests, Personal, Advisory Board: Boryung Pharmaceutical; Non-Financial Interests, Institutional, Product Samples: Chong Kun Dang Pharmaceutical. All other authors have declared no conflicts of interest.