LBA71 - A multi-centre open-label randomized phase II study of osimertinib with and without ramucirumab in TKI-naïve EGFR-mutant metastatic NSCLC (RAMOSE trial interim analysis)

Background

Osimertinib (osi) is the current first-line therapy for patients (pts) with metastatic EGFR-mutant NSCLC. Combination of anti-VEGF with EGFR inhibitors has a potential to prolong progression-free survival (PFS).

Methods

The RAMOSE trial (NCT03909334, HCRN LUN-18-335) is a randomized, open-label phase 2 study comparing osi 80mg PO daily + ramucirumab 10 mg/kg IV q3 weeks (Arm A) to osi alone (Arm B) for initial treatment of metastatic EGFR-mutant NSCLC with 2:1 randomization. The primary endpoint is PFS by investigators, secondary endpoints include best response rates (BRR), disease control rate (DCR), overall survival (OS), and safety. The stratification criteria for randomization were EGFR mutation type and presence of CNS metastasis.

Results

At data cut-off Aug 29, 2023, 160 pts consented, 147 pts received treatment, and 139 pts had at least one efficacy scan. The median follow up was 16.6 months (range 1.4-46.1). Among the 139 pts, 57 PFS events (37 progressions and 20 progressions followed by death) were observed, 32 in A and 25 in B. The median PFS was 24.8 (A) vs 15.6 (B) months (HR=0.55; 95%CI: 0.32-0.93; Log Rank p=0.023), 12-mon PFS rate was 76.7% (A) vs. 61.9% (B, p=0.026). BRRs and DCRs had no difference. For high risk gorup of 43 (31%) pts with L858R, PFS was 24.8 (A) vs 18.4 months (B, p=0.388); for 64 (46%) pts with CNS metastasis, PFS was 17.9 (A) vs 13.8 months (B, p=0.225). Any-grade (G) AEs occurred in 93% (A) and 87% (B) of pts. There were no G5 treatment-related AE (TRAE), one G4 TRAE (hyponatremia, A), 46% (A) vs. 35% (B) G3 TRAEs, including G3 hypertension at 28% (A) vs 7% (B) and decreased neutrophils at 21% (A) vs 23% (B). AE-related discontinuation was observed in13 pts (9.7% in A, 8.7% in B). Table: LBA71

Conclusions

Ramucirumab + osi significantly prolonged PFS compared to osi alone in EGFR-mutant NSCLC pts. The RAMOSE seems to be as efficacious as FLAURA2. Safety profile was in line with known safety of each drug.

Clinical trial identification

NCT03909334.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Eli Lilly.

Disclosure

X. Le: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck KGaA, Spectrum Pharmaceutics, Novartis, Boehringer Ingelheim, Eli Lilly, Hengrui, Janssen, Blueprint, Daiichi Sankyo, Regeneron, ArriVent, Abion, Pinetree therapeutics, AbbVie; Financial Interests, Institutional, Invited Speaker: Eli Lilly, EMD Serono, Regeneron, Janssen; Financial Interests, Institutional, Research Grant: Arrivent; Financial Interests, Institutional, Funding: Teligene. J.V. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly & Co., Janssen Pharmaceuticals, Boehringer-Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca, BioAlta, Sanofi, Spectrum Pharmaceuticals, GSK, Spectrum; Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Institutional, Other, International PI for clinical trials: AstraZeneca; Financial Interests, Institutional, Other, International PI for two clinical trials: Boehringer-Ingelheim; Financial Interests, Personal and Institutional, Other, Developed a drug: Spectrum; Financial Interests, Institutional, Coordinating PI: Takeda. All other authors have declared no conflicts of interest.