49P - Ramucirumab beyond progression plus TAS 102 in patients with advanced or metastatic adenocarcinoma of the stomach or the gastroesophageal junction, after treatment failure on a ramucirumab based therapy: Final results of the phase II RE-ExPEL study

Background

Based on results of prior trials (TAGS, REGARD, RAINBOW), it seems promising to combine ramucirumab (Ram) beyond progression (PD) with TAS-102 (trifluridine/tipiracil). The purpose of RE-ExPEL is to investigate the tolerability, safety and benefit of Ram beyond PD in combination with TAS-102 in advanced esophagogastric adenocarcinoma (EGA).

Methods

This is a multicenter, non-randomized, open-label investigator-initiated pilot trial. 20 Ram-pretreated patients (pts) with advanced EGA were enrolled to a maximum of 4 cycles of ramucirumab 8mg/kg every two weeks (days 1, 15; qd28) plus TAS-102 35 mg/m2/p.o. bid (d1-5 and d8-12; qd28). Primary endpoint (EP) was tolerability and toxicity, defining a positive trial if SAE rate according to CTCAE 5.0 will increase less than 30% (up to 55%) compared with results from TAGS (SAE-rate 43%). Secondary EPs are further safety data and efficacy data, OS, PFS and ORR.

Results

20 pts (20% female) were enrolled between Oct 2020 and Aug 2021, 20% gastric and 80% GEJ- cancers, 55% of pts with ECOG 0. Results of the final analysis showed that only 25% of pts had at least one SAE and the total no. of SAEs was 9, one with fatal outcome, all without relationship to systemic therapy and no SUSAR reported. RE-ExPEL was able to show a median OS of 9.07 mo (95% CI 5.42-10.09) and a DCR of 45%. 90% of pts got study medication in 3^rd line whereas 10% were even further line pts.

Conclusions

The safety data showed a favorable safety profile with a low rate of severe toxicity for Ram+TAS-102, maybe due to the long disease stabilization and therefore less tumor-associated symptoms. Regarding the primary safety endpoint, the trial was positive with even a numerically lower SAE rate compared with TAGS. Furthermore, RE-ExPEL was able to show very promising efficacy data for the combination Ram+TAS-102 with median OS of 9.07 mo. Ram+TAS-102 seems to be more effective than TAS-102 alone according to TAGS-trial respecting the limitation of the RE-ExPEL one-arm study design with only 20pts. The combination needs further evaluation in a randomized phase III trial.

Clinical trial identification

EudraCT 2020-001075-32, Trial release date: 10.03.2020.

Editorial acknowledgement

Legal entity responsible for the study

Institut für Klinische Krebsforschung IKF GmbH, Frankfurt, Germany.

Funding

Lilly.

Disclosure

T.O. Goetze: Financial Interests, Personal, Advisory Role: Lilly, MSD Oncology, Bayer, Servier, Roche, Novartis, Incyte, Foundation Medicine, Bristol Myers Squibb; Financial Interests, Personal, Funding: Deutsche Forschungsgemeinschaft, Gemeinsamer Bundesausschuss; Financial Interests, Institutional, Funding: Deutsche Krebshilfe, Lilly, AstraZeneca, Incyte; Financial Interests, Institutional, Speaker’s Bureau: Lilly. A. Stein: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, GBA Innovationsfond, Deutsche Krebshilfe, MSD, Roche, Sanofi, SERVIER; Financial Interests, Institutional, Advisory Role, and Speaker: Amgen, Bristol Myers Squibb, Daiichi Sankyo, Merck, MSD, Novartis, Servier. E. Goekkurt: Financial Interests, Personal, Advisory Role: MSD, Bristol Myers Squibb, Roche, Sanofi. S. Al-Batran: Financial Interests, Personal, Advisory Role: Lilly, Bristol Myers Squibb, Merck Sharp & Dohme, MacroGenics, Astra/Daichii; Financial Interests, Personal, Speaker’s Bureau: Lilly, AIO gGmbH, Bristol Myers Squibb, MCI Group; Financial Interests, Personal, Ownership Interest: Institut für Klinische Krebsforschung GmbH; Financial Interests, Personal, Funding: Celgene, Lilly, Medac, Hospira, Sanofi, German Cancer Aid, German Research Foudation, Federal Ministry of Education and Research, Roche, Vifor Pharma, Eurozyto, Ipsen, Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Immutep. All other authors have declared no conflicts of interest.