LBA83 - PECATI: A phase II trial to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab in pretreated advanced B3-thymoma and thymic carcinoma

Background

The standard treatment for patients with platinum refractory advanced B3-Thymoma (T) and thymic carcinoma (TC) has not yet been established. Both, lenvatinib and immune checkpoint blockers have shown clinically meaningful results in this setting. The phase 2 single-arm PECATI trial (NCT04710628) assesses the efficacy and safety of lenvatinib (L) plus pembrolizumab (P) in patients with advanced pre-treated B3-T and TC without autoimmune disorders.

Methods

Patients received L (20 mg orally daily) combined with P (200 mg iv infusion once every 3 weeks) in 3-week cycles until disease progression, unacceptable toxicity, or a maximum treatment duration of 35 cycles. The primary endpoint is the 5-month progression-free survival (5-PFS) rate (H₀: 5-PFS of ≤50%; H₁: 5-PFS of > 68.6%) assessed by investigator. Secondary endpoints encompass objective response rate (ORR), disease control rate (DCR), and overall survival (OS), and safety (grade ≥3 treatment related adverse events, TRAEs).

Results

From 09/2021 to 02/2024, 43 patients were enrolled: median age 57 years (33-80); 84% had a TC; Masaoka Koga IVA / B (35% / 65%) with ≥3 metastatic sites in 56% of patients (including 37% with liver metastases). The median number of target lesions was 2 and median sum of target lesions of 86 mm (11-204). The number of previous lines were: 1 (54%), 2 (39%) and >2 (7%). PD-L1 expression (22C3, n= 32) <1%: 53%, 1-49%: 31%; ≥50%: 16%. The study met its primary endpoint: 5-PFS rate of 91%, with 1-year PFS of 62%. The confirmed ORR was 21% with a confirmed DCR of 67%. After a median follow up of 10.6 months, median OS was not estimated, and 1-year OS was of 85%. The rate of grade ≥3 TRAEs was 34.9%, being the most common diarrhea (7%), hypertension (7%), and hepatic cytolysis (5%). Serious grade ≥3 TRAEs occurred in 16% of patients (7/43), including 1 (2.3%) patient with myocarditis, and 1 (2.3%) patient with pneumonitis. There were no treatment-related deaths.

Conclusions

Lenvatinib combined with pembrolizumab is a potential standard treatment in pre-treated advanced B3-thymoma and thymic carcinoma. Toxicity profile is manageable but close monitoring is advised.

Clinical trial identification

NCT04710628; EudraCT: 2020-000397-18.

Editorial acknowledgement

Legal entity responsible for the study

MEDSIR.

Funding

Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme LLC. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme LLC.

Disclosure

J. Remon Masip: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Janssen, Merck, Takeda; Financial Interests, Personal, Other, Travel, accomodation: Ose Immunotherapeutics; Financial Interests, Institutional, Advisory Board: Edi Mack; Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. P. Bironzo: Financial Interests, Institutional, Research Grant: Pfizer, Roche; Non-Financial Interests, Advisory Role: Janssen, Regeneron, Pierre Fabre, Seagen. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. L. Bigay-Game: Financial Interests, Speaker, Consultant, Advisor: MSD, BMS, AstraZeneca, Takeda; Financial Interests, Other, Consultancy: Janssen, Roche; Financial Interests, Invited Speaker: Pfizer, Sanofi, Léopharma, Viatris. O.J. Juan Vidal: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, Merck Sharp & Dohme, Takeda; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Non-Financial Interests, Institutional, Funding: AstraZeneca. J. de Castro Carpeño: Financial Interests, Speaker, Consultant, Advisor: AstraZeneca, Hoffmann -La Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Amgen; Financial Interests, Advisory Role: Boehringer Ingelheim, Johnson and Johnson, Lilly, Sanofi, Takeda, Gilead, GSK; Financial Interests, Invited Speaker: Pierre Fabre. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Boehringer, Pfizer, Novartis, Sanofi, Janssen, AstraZeneca, Amgen, Novartis, Merck, Janssen, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS, Amgen, Novartis, Sanofi, Merck; Non-Financial Interests, Principal Investigator, PI of Investigator Initiated Trial (PEERS) sponsored by MSD: MSD. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi; Financial Interests, Personal, Local PI: Roche. S. Cousin: Financial Interests, Advisory Board: Amgen, AbbVie, Lilly, Roche. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Takeda, Janssen, Cassen Recordati, Bms, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer, Takeda, Helsinn; Financial Interests, Institutional, Funding: BMS, AstraZeneca, Roche; Non-Financial Interests, Leadership Role, Board Member: Associacio Contra El Cancer Barcelona. M. Diaz: Financial Interests, Institutional, Full or part-time Employment: MEDSIR. A. Meya: Financial Interests, Institutional, Full or part-time Employment: MEDSIR. D. Alcalá-López: Financial Interests, Institutional, Full or part-time Employment: MEDSIR. A.G. Sanz: Financial Interests, Institutional, Full or part-time Employment: MEDSIR. L. Righi: Financial Interests, Speaker, Consultant, Advisor: Roche, Novartis, Eli Lilly, AstraZeneca, BMS. S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Eli Lilly, Novartis, BeiGene, Amgen, Thermo Fisher; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen, J&J; Financial Interests, Institutional, Coordinating PI, IIT: MSD, BI; Financial Interests, Institutional, Coordinating PI: AZ, AMG, Eli Lilly, Sanofi, J&J, Roche; Non-Financial Interests, Leadership Role, president of this european advocacy: WALCE; Non-Financial Interests, Member: IASLC, AIOM, ASCO. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BeiGene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd, 4D Pharma, AbbVie, Da Voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD; Financial Interests, Institutional, Local PI: AbbVie, Amgen, Blueprint Medicines, Daiichi Sankyo, Pfizer, Roche-Genentech, Turning Point Therapeutics, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Ose Immunotherapeutics, Sanofi, Taiho; Financial Interests, Institutional, Steering Committee Member: BeiGene, GSK, Janssen, Takeda, Genmab; Financial Interests, Institutional, Funding: Cristal Therapeutics. All other authors have declared no conflicts of interest.