Background

Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. FORWARD I, a phase III study, evaluated the safety and efficacy of MIRV compared to chemotherapy in pts with PROC.

Methods

Pts with PROC, 1-3 prior lines of therapy, and FRα positivity by immunohistochemistry (stratified by predefined medium or high expression) were enrolled. Pts were randomized 2:1 to MIRV (6 mg/kg, adjusted ideal body weight) once every 21 days or investigators’ choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival (PFS) by blinded independent review committee, in both the intention-to-treat (ITT) population (medium and high FRα expression) and, separately, in pts with high FRα. Secondary endpoints included objective response rate (ORR) and overall survival (OS). Median follow-up time was 12.5 months.

Results

Of 366 pts randomized, 248 received MIRV and 118 chemotherapy. Baseline characteristics were well balanced across arms. In the ITT population, the PFS hazard ratio (HR) was 0.981 (median PFS of 4.1 vs 4.4 months for MIRV and chemotherapy, respectively). For the high FRα pt subset (n = 218), additional outcomes favored MIRV over chemotherapy: PFS HR of 0.693 (4.8 vs 3.3 months; p = 0.049, not significant by Hochberg procedure), ORR (24% vs 10%), and interim OS (83/213 events (34%); median not reached vs 11.8 months; HR, 0.618). The most common adverse events (AEs) observed with MIRV were nausea (54%), diarrhea (44%), and blurred vision (43%). Fewer high grade (≥ 3) events, dose modifications, and discontinuations due to AEs were seen with MIRV.

Conclusions

While the study did not meet the primary endpoint, promising and consistent efficacy measures were observed in the predefined subset of high FRα PROC pts treated with MIRV. Along with favorable tolerability and differentiated safety, these findings suggest a favorable benefit-risk profile for MIRV in this biomarker-defined and difficult-to-treat population.

Clinical trial identification

NCT02631876.

Legal entity responsible for the study

ImmunoGen, Inc.

Funding

ImmunoGen, Inc.

Disclosure

K.N. Moore: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Aravive. A. Oaknin: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: ImmunoGen. D. Lorusso: Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy: Merrimack. C.G. Murphy: Advisory / Consultancy: Janssen; Advisory / Consultancy: Roche; Advisory / Consultancy: Nordic Pharma; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Pfizer. J.A. Konner: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: ImmunoGen. M. Prasad Hayes: Research grant / Funding (institution): AstraZeneca. S.K. Kim: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy: Cytomx; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas/Agensys. J. Wang: Full / Part-time employment: ImmunoGen Inc. P. Pautier: Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. M.J. Birrer: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Merck Sharp & Dome; Advisory / Consultancy: Genentech USA; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

Background

Low-grade serous carcinoma of the ovary/peritoneum (LGSOC) is a rare subtype, accounting for 5-10% of all serous cancers, and is characterized by alterations in the MAPK pathway, relative chemoresistance, and prolonged overall survival (OS) compared to high-grade serous carcinoma. NRG Oncology in the US and the National Cancer Research Network (NCRN) in the UK collaborated on a phase II/III trial to assess the efficacy of a MEK inhibitor trametinib (TRAM) compared to physician’s choice standard of care (SOC) in recurrent LGSOC.

Methods

Patients (pts) were randomized 1:1 to receive either TRAM 2 mg daily or 1 of 5 SOC options (weekly paclitaxel, PLD, topotecan, letrozole, or tamoxifen) until disease progression. Pts who progressed on SOC were allowed to crossover to TRAM. The primary objective tested the progression-free survival (PFS) superiority of TRAM vs SOC. Secondary objectives included toxicity, QoL, and objective response rate (ORR) by RECIST 1.1. Exploratory objectives were OS and PFS and ORR after crossover. PFS and OS curves were estimated using the Kaplan-Meier method and compared by a 1-sided, α = 0.025 log-rank test.

Results

260 pts (48.1% had >3 prior lines of therapy) were enrolled between Feb 2014 and Apr 2018. Median follow-up was 31.4 months (mo). PFS was significantly improved for TRAM compared to SOC (median, 13.0 vs 7.2 mo; HR 0.48; 95% CI, 0.36-0.64; P < .0001). ORR was 26.2% for TRAM vs 6.2% for SOC (OR 5.4; 95% CI, 2.39-12.21; P< .0001). Response duration for TRAM was significantly better than for SOC (median, 13.63 mo; 95% CI, 8.08-18.76; vs 5.88 mo; 95% CI, 2.76-12.19). Preliminary analysis of QoL patient reported outcomes shows no significant therapy effects. Main Grade >3 AE in TRAM vs SOC were hematologic toxicity (13.4% vs 9.4%), GI toxicity (27.6% vs 29%), skin toxicity (15% vs 3.9%), and vascular toxicity (18.9% vs 8.6%). Median OS for TRAM vs SOC was 37.0 mo (95% CI, 30.3-NE) vs 29.2 mo (95% CI, 23.5-51.6) (HR 0.75; 95% CI, 0.51-1.11). For 88 pts who crossed over to TRAM, median PFS = 10.8 mo (95% CI, 7.3-12.0), and ORR = 15% (95% CI, 0.07-0.22).

Conclusions

Compared to physician’s choice SOC, TRAM was associated with significantly improved PFS and ORR in women with recurrent LGSOC.

Clinical trial identification

NCT02101788.

Legal entity responsible for the study

National Cancer Institute (NRG Oncology).

Funding

National Cancer Institute (US) and Novartis.

Disclosure

W. Brady: Full / Part-time employment: Sarah Cannon Development Innovations. R.L. Coleman: Advisory / Consultancy, Leadership role, Research grant / Funding (self), Non-remunerated activity/ies: AbbVie; Honoraria (self), Advisory / Consultancy: aravive; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche Genentech; Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Novartisjavascript:%20create_table_line(’1’,%20new%20Array(’ent’,%20’des’,%20’tor’));; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Merck; Honoraria (self), Advisory / Consultancy, Non-remunerated activity/ies: Immunogen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro/GSK; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Genmab; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Gamamab; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Oncomed; Honoraria (self), Advisory / Consultancy: Agenus; Research grant / Funding (self), Research grant / Funding (institution): NCI-SPORE. K.N. Moore: Honoraria (institution), Advisory / Consultancy: Clovis. S. Banerjee: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro; Honoraria (self): Clovis; Honoraria (self): Merck Sereno; Honoraria (self): Seattle Genetics; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): PharmaMar; Research grant / Funding (institution): Janssen Cilag; Honoraria (self), Travel / Accommodation / Expenses: Gamamabs. A.A. Secord: Research grant / Funding (institution): AbbVie, Amgen, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Eisai, Endocyte, Exelixis, Incyte, Merck, PharmaMar, Immutep Ltd, Roche/Genentech, Seattle Genetics, Inc, TapImmune and Tesaro; Honoraria (self): Aravive, AstraZeneca, Clovis, Janssen/Johnson & Johnson, Merck, Mersana, Oncoquest, Roche/Genentech, and Tesaro . D.M. O’Malley: Honoraria (self), Advisory Board: Genelux; Honoraria (self), Research grant / Funding (institution), Advisory Board: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GOG Foundation; Honoraria (self): NCCN; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Immunogen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Advisory board, Steering Committee: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Advisory board: Abbie, Iovance ; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), US PI/Steering Committee: Novocure; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Advisory board, Steering Committee: Tesaro; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Advisory board, steering Committee: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Advisory board, PI, Steering Committee: Agenus; Honoraria (self), Advisory / Consultancy, Advisory board: OncoQuest; Honoraria (self), Advisory / Consultancy, Advisory board: Ambry; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): AMGEN, BMS; Research grant / Funding (institution): Array Biopharma, inVentiv ; Research grant / Funding (institution): Janssen, Tracon; Research grant / Funding (institution): EMD Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Advisory board: Leap Therapeutics. O. Dorigo: Advisory / Consultancy, Speaker Bureau / Expert testimony: Tesaro; Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Merck. S. Gaillard: Research grant / Funding (institution): Pfizer, Bristol-Myers Squibb, Genentech/Roche, Gradalis, Iovance Biotherapeutics, Merck, PharmaMar, TetraLogic Pharmaceuticals, AbbVie; Advisory / Consultancy: AstraZeneca, Immunogen. C. Gourley: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Nucana; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Foundation One; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Sierra Oncology; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Cor2ED; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Aprea. All other authors have declared no conflicts of interest.

Background

High unmet medical need persists in pts with R/M cervical cancer; median overall survival (OS) is < 17 mo after 1L therapy with few options in 2L. Per current guidelines, pts whose tumors express programmed death ligand 1 (PD-L1) are eligible for pembrolizumab in the 2L setting. CheckMate 358 (NCT02488759) is an ongoing open-label, multi-cohort, phase I/II study of Nivo +/- Ipi in virus-associated cancers regardless of PD-L1 expression. Here we report an interim analysis of pts with R/M cervical cancer, with or without prior systemic therapies (PST), receiving Nivo + Ipi.

Methods

Eligible pts had R/M cervical cancer treated with 0-2 PST. Pts were randomized to Nivo 3mg/kg Q2W + Ipi 1mg/kg Q6W (Combo A), or Nivo 1mg/kg + Ipi 3mg/kg Q3W for 4 doses followed by Nivo 240mg Q2W (Combo B), for ≤24 mo until progression or unacceptable toxicity. Primary endpoint: investigator-assessed objective response rate (ORR) by RECIST 1.1; secondary endpoints: OS, progression-free survival (PFS) and duration of response.

Results

Median follow-up was 10.7 mo [Combo A, n = 45] and 13.9 mo [Combo B, n = 46]. ORR was higher in Combo B vs Combo A without PST (46% vs 32%) and with PST (36% vs 23%; Table). Median PFS in Combo A was 13.8 mo (95% CI 2.1, not reached [NR]) in pts without PST and 3.6 mo (1.9, 5.1) in pts with PST. Median PFS in Combo B was 8.5 mo (3.7, NR) without PST and 5.8 mo (3.5, 17.2) with PST. Median OS in Combo A was NR (17.4, NR) in pts without PST and 10.3 mo (7.9, 15.2) in pts with PST. Median OS in Combo B was NR without PST (13.9, NR) and 25.4 mo with PST (17.5, NR). Incidence of all/grade 3–4 treatment-related adverse events (AEs) was 80.0%/28.9% in Combo A and 82.6%/37.0% in Combo B. No new safety signals were identified.Table:

LBA62

Conclusions

These results suggest clinical benefit from two regimens of Nivo + Ipi in pts with R/M cervical cancer regardless of PD-L1 status. Combo B had notable efficacy in pts with PST. AEs were manageable and consistent with previous reports of Nivo + Ipi therapy.

Clinical trial identification

NCT02488759.

Editorial acknowledgement

Writing and editorial assistance was provided by Brooke Middlebrook of Evidence Scientific Solutions Inc, and funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb, Princeton, NJ, USA.

Funding

Bristol-Myers Squibb, Princeton, NJ, USA.

Disclosure

R.W. Naumann: Research grant / Funding (institution): Bristol-Myers Squib; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): OncoMed; Advisory / Consultancy, Research grant / Funding (institution): SutroBio. A. Oaknin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, grant for VHIO: Pharma Mar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, grant for VHIO & VHIR: Clovis Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, grant for VHIO: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), grant for VHIO: Immunogen; Advisory / Consultancy: Genmab; Research grant / Funding (institution), VHIR: Abbie Deutchland; Research grant / Funding (institution), VHIO: Ability Pharmaceuticals; Research grant / Funding (institution), VHIO: Advaxis Inc; Research grant / Funding (institution), VHIR: Aeterna Zentaris; Research grant / Funding (institution), VHIR: Amgen SA; Research grant / Funding (institution), VHIO: Aprea Therapeutics AB; Research grant / Funding (institution), VHIO: Eisai Ltd; Research grant / Funding (institution), VHIO: F. Hoffmann - La Roche Ltd. ; Research grant / Funding (institution), VHIO: Regeneron Pharmaceuticals; Research grant / Funding (institution), VHIO: Merck Sharp & Dohme de España SA; Research grant / Funding (institution), VHIO: Millennium Pharmaceuticals Inc.. T. Meyer: Advisory / Consultancy: Beigene; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): BTG; Advisory / Consultancy: Eisai; Advisory / Consultancy: Ipsen; Research grant / Funding (institution): Bayer; Travel / Accommodation / Expenses, consultancy: BMS. C. Lao: Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Research grant / Funding (self): Genentech; Research grant / Funding (self): Merck; Research grant / Funding (self): Dynavax; Research grant / Funding (self): Novartis; Advisory / Consultancy: Immunocore. Y. Bang: Advisory / Consultancy: Hanmi; Advisory / Consultancy, Research grant / Funding (institution): Genexine; Advisory / Consultancy: Samyang Biopharm; Advisory / Consultancy, Research grant / Funding (institution): GreenCross; Advisory / Consultancy, Research grant / Funding (institution): BeiGene; Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Daiichi-Sankyo; Advisory / Consultancy: Taiho; Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): Curis; Research grant / Funding (institution): Taiho; Research grant / Funding (institution), Ono, CKD Pharma, Genexine Grant to Institution.: Takeda. V. Boni: Advisory / Consultancy: Loxo therapuetics; Advisory / Consultancy: Ideaya. W.H. Sharfman: Research grant / Funding (institution), personal fees: BMS; Research grant / Funding (institution), personal fees: Merck; Research grant / Funding (institution), personal fees: Novartis; Advisory / Consultancy: Iovance; Advisory / Consultancy: Regeneron. K. Harano: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Chugai; Advisory / Consultancy: Eizai; Advisory / Consultancy: Taiho; Advisory / Consultancy: Takeda. C.H. Chung: Honoraria (self), Received honorarium for ad hoc scientific advisory board participation: Bristol-Myers Squibb. S.L. Topalian: Shareholder / Stockholder / Stock options, Licensing / Royalties: Aduro Biotech; Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Compugen; Advisory / Consultancy, Shareholder / Stockholder / Stock options: DNAtrix; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Dragonfly Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: ERVAXX; Advisory / Consultancy, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: Five Prime Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: FLX Bio; Shareholder / Stockholder / Stock options: Jounce Therapeutics; Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Potenza Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tizona Therapeutics; Advisory / Consultancy, Shareholder / Stockholder / Stock options: WindMIL; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Dynavax; Advisory / Consultancy, Licensing / Royalties: lmmunomic Therapeutics; Advisory / Consultancy: Janssen Oncology; Advisory / Consultancy: MedImmune; Advisory / Consultancy: Merck; Research grant / Funding (institution), Travel / Accommodation / Expenses, Licensing / Royalties: Bristol-Myers Squibb. T. Chen: Licensing / Royalties: Combination therapy with anti-IL-8 antibodies and anti-PD-1 antibodies for treating cancer. B. Li: Full/Part-time employment: Bristol-Myers Squibb. A.M. Barrows: Full / Part-time employment: Bristol-Myers Squibb. A. Horvath: Full / Part-time employment: Bristol-Myer Squibb. K.N. Moore: Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Immunogen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Tesaro; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Janssen; Advisory / Consultancy: Aravive; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Onco Med; Advisory / Consultancy: Samumed; Research grant / Funding (self), Research grant / Funding (institution): Lilly; Advisory / Consultancy: Eisai. All other authors have declared no conflicts of interest.

Background

LEN is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT. PEMBRO is an anti-PD-1 antibody. We report final results of a cohort of patients (pts) with metastatic EC (data cutoff, Jan. 10, 2019) as part of an ongoing phase 1b/2 study evaluating LEN + PEMBRO in pts with selected solid tumours.

Methods

In this cohort of a multicenter, open-label study, pts with histologically confirmed metastatic EC and measurable disease who received ≤2 prior chemotherapies (unless discussed with the sponsor) were administered LEN (20 mg PO QD) plus PEMBRO (200 mg IV Q3W). Tumour assessments for the primary phase 2 endpoint (objective response rate at 24 weeks [ORR_WK24]) and secondary endpoints were evaluated by investigators per immune-related (ir)RECIST. Secondary endpoints included ORR, progression-free survival, overall survival, and duration of response. Tumour responses were also assessed by independent imaging reviewers per irRECIST, RECIST 1.1, and modified RECIST 1.1, and by investigators per mRECIST 1.1.

Results

At data cutoff, 108 pts with previously treated (1 regimen: 53%; >1 regimen: 47%) EC (endometrioid: 51%; serous: 32%; FIGO grade 3: 70%) were enrolled and had a median follow-up of 18.7 months. 13% of pts had high microsatellite instability (MSI-H) or mismatch-repair deficient (dMMR) status. Efficacy outcomes are summarized in the table. Treatment-related adverse events (TRAEs) occurred in 105 (97%) pts (97 [90%] ≤ grade 3, 8 [7%] ≥ grade 4). TRAEs led to study-drug interruption of one or both drugs in 78 (72%) pts and dose reductions of LEN in 70 (65%) pts; 20 (19%) pts discontinued one or both drugs due to a TRAE. The most common ≥ grade 3 TRAEs were hypertension (32%), fatigue (8%), and diarrhea (7%).

Conclusions

The LEN + PEMBRO combination showed promising antitumor activity in metastatic EC regardless of MSI/MMR status. Treatment was generally well tolerated, and no new safety signals emerged. A phase 3 study in advanced EC is underway (NCT03517449).Table: 994O

Clinical trial identification

NCT02501096.

Editorial acknowledgement

Jeffrey K. Bratz, PhD of Oxford PharmaGenesis, Newtown, PA was funded by Eisai Inc.

Legal entity responsible for the study

Eisai Inc.

Funding

Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

V. Makker: Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Eisai; Honoraria (self), Non-remunerated activity/ies: Merck; Non-remunerated activity/ies: Lilly; Honoraria (self), Non-remunerated activity/ies: Karyopharm; Honoraria (self), Non-remunerated activity/ies: Takeda; Non-remunerated activity/ies: Genentech. M.H. Taylor: Research grant / Funding (institution): BioAlta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Array Biopharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: LOXO; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Blueprint; Honoraria (self), Advisory / Consultancy: Arquele; Honoraria (self), Advisory / Consultancy: Novartis. C. Aghajanian: Advisory / Consultancy: Tesaro; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Research grant / Funding (self): Clovis; Honoraria (self): Mateon Therapeutics; Advisory / Consultancy: Cerulean Pharma; Research grant / Funding (self): Genentech. A. Oaknin: Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution), Travel / Accommodation / Expenses: Clovis Oncology; Honoraria (self), Research grant / Funding (institution): Tesaro; Honoraria (self), Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Eisai Ltd.; Research grant / Funding (institution): Merck Sharp & Dohme de España SA; Honoraria (self): Genmab; Research grant / Funding (institution): AbbVie Deutschland; Research grant / Funding (institution): Millennium Pharma; Research grant / Funding (institution): Regeneron Pharmaceuticals; Research grant / Funding (institution): Ability Pharmaceuticals; Research grant / Funding (institution): Advaxis Inc; Research grant / Funding (institution): Aeterna Zentaris; Research grant / Funding (institution): Amgen SA; Research grant / Funding (institution): Aprea Therapeutics AB; Research grant / Funding (institution): F. Hoffman - La Roche Ltd. M. Romeo Marin: Advisory / Consultancy: Tesoro; Advisory / Consultancy, Non-remunerated activity/ies: Roche; Speaker Bureau / Expert testimony: AstraZeneca. M.S. Brose: Honoraria (self): Eisai. D.E. Stepan: Full / Part-time employment: Formerly of Eisai Inc. C.E. Dutcus: Leadership role, Full / Part-time employment: Eisai Inc. J. Wu: Full / Part-time employment: Eisai Inc. E.V. Schmidt: Full / Part-time employment: Merck & Co Inc. R.J. Orlowski: Full / Part-time employment: Merck & Co Inc. P. Sachdev: Full / Part-time employment: Eisai Inc. R. Shumaker: Full / Part-time employment: Eisai Inc. A. Casado Herraez: Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar. All other authors have declared no conflicts of interest.