788P - 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 targeting of angiogenic and immune pathways is an emerging strategy in CCGC in view of its unique molecular and microenvironmental features.

Methods

LARA enrolled recurrent CCGC patients (pts) in Singapore and South Korea with progression on ≥1 platinum-based chemotherapy and no prior immunotherapy exposure. 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). ≥2/15 responders were required to progress to stage 2. The PEP is met if ≥6/25 efficacy evaluable pts respond to PL.

Results

In total, 27 pts were treated between 26/3/21-10/11/23 (Chinese: 12, Korean: 12, Malay: 2, Filipino: 1). Median age was 52 years (range 40-72), ECOG PS (0: 13, 1: 14), 24/27 (88.9%) ovarian primary. Median of 2 prior therapy lines (range 1-4). 17/27 (62.9%) pts had prior bevacizumab/anti-antiangiogenics. 16/27 (59.2%) pts had progressed after platinum therapy-free interval (TFIp) <6 months. All pts were proficient in MMR protein expression/microsatellite stable (pMMR/MSS). Median duration of follow-up was 47 wks (interquartile range 28.4-107.7). 25 pts were evaluable for efficacy. 11/25 pts had confirmed response in the first 24 wks, ORR_24wks 44.0% (95% CI 24.4-65.1). Median PFS was 23.4 wks (95% CI 4.4-42.4), PFS at 12 and 24 wks were 60% (95% CI 38.4-76.1) and 48% (95% CI 27.8-65.6), respectively. Confirmed GCIG CA125 response occurred in 8/13 (61.5%; 95% CI 31.5-86.1) OCCC pts evaluable by GCIG criteria. Common (≥5%) grade ≥3 treatment-related adverse events were hypertension (6/27), AST elevation (3/27), ALT elevation (2/27), thrombocytopenia (2/27). 2/27 pts discontinued treatment due to toxicity.

Conclusions

PL demonstrated impressive anti-tumor activity without unexpected toxicity in pMMR/MSS recurrent CCGC, including pts with progression after short TFIp and prior anti-angiogenic exposure. PL is a viable treatment strategy for this area of unmet clinical need.

Clinical trial identification

NCT04699071.

Editorial acknowledgement

Legal entity responsible for the study

Asia-Pacific Gynecologic Oncology Trials Group.

Funding

MSD MISP (Drug-only) and Pangestu Family Foundation Gynaecological Cancer Research Fund.

Disclosure

N. Ngoi: Financial Interests, Institutional, Advisory Board: MSD, Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD; Non-Financial Interests, Institutional, Product Samples: iOnctura, Cyclacel Ltd; Non-Financial Interests, Member: Gynecologic Cancer Group Singapore. 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. J.J. Chan: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Merck Sharp & Dohme, Novartis, Pfizer, DKSH Singapore; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Merck Sharp & Dohme, Eisai; Financial Interests, Personal, Writing Engagement: GSK; Financial Interests, Personal, Other, Conference fee: Merck KGaA, AstraZeneca, Novartis; Non-Financial Interests, Other, Track Chair, Breast Track, 7th Annual Scientific Meeting 2022: Singapore Society of Oncology; Non-Financial Interests, Advisory Role, Member, International Steering Committee (Gynecologic Oncology): Japanese Society of Medical Oncology; Non-Financial Interests, Other, Member, Special Task Force on Personalized Medicine: Asian Society of Gynecologic Oncology; Non-Financial Interests, Member: Singapore Society of Oncology; Non-Financial Interests, Leadership Role, Secretary: Gynecologic Cancer Group Singapore; Non-Financial Interests, Leadership Role, Co-opted Member, Executive Board: Chapter of Medical Oncologists, College of Physicians, Academy of Medicine Singapore. 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, Leadership Role, Ex society president: Gynecologic Cancer Group Singapore; Non-Financial Interests, Member of Board of Directors: Gynaecologic Cancer Intergroup (GCIG); Non-Financial Interests, 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.