LBA98 - Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial

Background

Thymic carcinoma (TC) is a rare tumor with aggressive and poorly responsive behavior. In advanced lines, antiangiogenics showed activity in TC. Ramucirumab (R) is a VEGF2 inhibitor monoclonal antibody already approved for other solid tumors. RELEVENT trial was design to assess activity and safety of the combination of R plus carboplatin (CBDCA) and paclitaxel (PTX) as first line treatment in patients (pts) with advanced TC.

Methods

This academic open-label single arm phase II trial was conducted within the Italian network TYME. Eligible pts had naive advanced TC (pathological diagnosis was centrally reviewed). All pts received R 10 mg/kg, CBDCA AUC5 and PTX 200 mg/m2 d1q21 for 6 cycles, followed by R 10 mg/kg maintenance until disease progression or intolerable toxicity. The trial was conceived with a Green-Dahlberg 2-stage design, 30 pts were analyzed in the 1^st stage (null hypothesis ORR 20%). In case of at least 5 responses, further 25 pts could have been added in the 2^nd stage. The primary endpoint was ORR. DCR, PFS, OS and safety were secondary endpoints. A centralized radiologic review was performed.

Results

From 11/2018 to 06/2023, 52 pts were screened and 37 were enrolled. Median (m) age was 60.5 years, 26 (70.3%) pts were male and 32 (86.5%) had stage IVB disease. ECOG PS was 0 in 26 (70%) and 1 in 11 (30%) pts; 35 pts were assessable for the primary endpoint ORR. At the 1^st stage, ORR (by investigator assessment) was 80% [95%CI 63.1-91.6] with DCR of 100% [95%CI 90-100]. At the centralized radiological review on 33/35 evaluable pts, ORR was 57.6% [95%CI 39.2-74.5], with 19 pts (57.6%) having a PR and 14 (42.4%) a SD, DCR was 100% [95%CI 89-100]. After a m follow up of 31.6 months [21.6-40.5], mPFS was 18.1 [95%CI 10.5-52.3] and mOS 43.8 [95%CI 22.5-NE] months. Of 35 pts, 28 (80%) experienced at least one treatment related adverse event (AE), 45.7% were G3 or more, (hypertension 8.8% and neutropenia 20% were the most common).

Conclusions

In previously untreated advanced TC, the addition of R to CBDCA and PTX showed highest activity compared to historical controls, with manageable safety profile. Despite the small number of pts, given the rarity of the disease, these results support the use of this combination as first line treatment in TC.

Clinical trial identification

NCT03921671.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale dei Tumori.

Funding

AIFA - Lilly.

Disclosure

C. Proto: Financial Interests, Personal and Institutional, Other: BMS and MSD. F.G.M. De Braud: Financial Interests, Personal and Institutional, Other: Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, Eli Lilly, F. Hoffmann-La Roche, Ignyta, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer.. R. Berardi: Financial Interests, Advisory Role: AZ, BOERINGHER, MSD, LILLY, Roche, Amgen, GSK, EISAI, BMS. P.A. Zucali: Financial Interests, Advisory Role: Merck Sharp & Dohme (MSD), Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer. M.C. Garassino: Financial Interests, Advisory Role: AstraZeneca, MSD International GmbH, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda. G. Lo Russo: Financial Interests, Invited Speaker: Eli Lilly, BMS, Italfarmaco, Novartis, AstraZeneca, Merck Sharp and Dohme, Takeda, Amgen, F. Hoffmann-La Roche, Sanofi, Pfizer, GSK. All other authors have declared no conflicts of interest.