LBA8 - Preliminary efficacy of pembrolizumab plus lenvatinib (PL) in recurrent clear cell gynecological cancer (CCGC): Phase II LARA trial (GCGS-OV4/ APGOT-OV3)

Background

Recurrent CCGC is associated with poor prognosis and low response rates to chemotherapy. Combined anti-angiogenic and immune checkpoint blockade is a rational strategy in CCGC in view of its unique gene expression profile and immune microenvironment. PL has potential to reprogram tumor-associated macrophages and enhance cytotoxic T cell response. We investigate the efficacy of PL in recurrent CCGC.

Methods

LARA is a phase II, academic trial conducted in Singapore and South Korea. Recurrent CCGC patients (pts) with progression on ≥1 prior platinum-based chemotherapy and no prior immunotherapy exposure were eligible. All pts received IV pembrolizumab 200mg on day 1 plus oral lenvatinib 20 mg daily, q21 days. LARA followed a Simon 2-stage minimax design. The primary endpoint (PEP) was objective response rate (RECIST1.1) at 24 weeks (ORR_24wks)(H₀≤10%; H₁≥30%; 5% 1-sided α; 80% power). 15 patients were required for stage 1, ≥2/15 responders to PL were required to progress to stage 2. A total of 25 evaluable pts are to be recruited in total. The study will meet its PEP if ≥6/25 pts respond to PL.

Results

From 26/3/21-12/4/23, 15 evaluable pts (Chinese: 8, Korean: 5, Malay: 2) were enrolled to stage 1. Median age was 58 years (range 41-72), ECOG PS (0: 6, 1: 9), 12/15 (80%) ovarian primary. Median of 1 prior therapy lines. 8/15 (53.3%) pts received prior bevacizumab or anti-antiangiogenic therapy. The median duration of follow-up was 48.9 weeks (IQR 32.3-not reached). 4/15 pts achieved confirmed objective response in the first 24 weeks (ORR_24wks 26.7%; exact binomial 95% CI 7.8-55.1). Confirmed CA125 response (GCIG criteria) occurred in 9/15 (60%, 95% CI 32.3– 83.7) pts. The median PFS was 12 weeks (95% CI 5.4-24.4), PFS at 12 and 24 weeks were achieved in 46.7% (95% CI 21.2-68.7) and 33.3% (95% CI 12.2-56.4) of pts, respectively. The efficacy boundary to proceed to stage 2 was met. Grade ≥3 treatment-related adverse events were hypertension (4/15), hyponatremia (2/15), rash (2/15), adrenal insufficiency (1/15), anemia (1/15), mucositis (1/15), thrombocytopenia (1/15).

Conclusions

PL showed promising efficacy and acceptable safety in recurrent CCGC pts. Final results at trial completion will be reported.

Clinical trial identification

NCT04699071.

Editorial acknowledgement

Legal entity responsible for the study

Asia-Pacific Gynecologic Oncology Trials Group (APGOT).

Funding

MSD MISP (Drug-only).

Disclosure

N.Y. Ngoi: Financial Interests, Institutional, Advisory Board: MSD, AstraZeneca, Merck/Pfizer; Financial Interests, Institutional, Invited Speaker: MSD, Japanese Society of Gynecologic Oncology; Financial Interests, Institutional, Speaker’s Bureau: Asian Society of Gynecologic Oncology. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: BeiGene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. D.S. Tan: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Merck Serono, Roche, Eisai, GSK, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, MSD, Eisai, Roche, Genmab, GSK, Boehringer Ingelheim; Financial Interests, Personal, Stocks/Shares: Asian Microbiome Library (AMiLi); Financial Interests, Institutional, Research Grant: Roche, Bayer, Karyopharm Therapeutics, AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Bergen Bio; Financial Interests, Institutional, Local PI: Zeria Pharmaceutical Co Ltd., Bayer, Byondis B.V.; Non-Financial Interests, Personal, Leadership Role, Ex society president: Gynecologic Cancer Group Singapore; Non-Financial Interests, Personal, Member of Board of Directors: Gynaecologic Cancer Intergroup (GCIG); Non-Financial Interests, Personal, Leadership Role, Ex- Chair: Asia-Pacific Gynecologic Oncology Trials Group (APGOT); Non-Financial Interests, Institutional, Product Samples, Research Study: MSD, Eisai, AstraZeneca, Cyclacel Pharmaceuticals. All other authors have declared no conflicts of interest.