Phase 1 study of ramucirumab (R) plus durvalumab (D) in patients (pts) with locally advanced and unresectable or metastatic gastrointestinal or thoracic malignancies (NCT02572687); Phase 1a results

Abstract

Aim/Background: Simultaneously targeting angiogenesis and immunosuppression demonstrates a synergistic antitumor effect in preclinical models. Preliminary safety results from the phase 1a portion of this study are reported for the NSCLC, G/GEJ, and HCC cohorts. Methods: Eligible pts with advanced NSCLC, G/GEJ, or HCC who progressed on prior systemic therapy were enrolled. Two dosing schedules will be evaluated in the Phase 1a/ DLT observation phase following 6+3 design: R (10 mg/kg intravenous [IV]) and D (1125mg IV) Q3W (21‐day cycle) for NSCLC, and R (8 mg/kg IV) and D (750 mg IV) Q2W (28‐day cycle) for G/GEJ and HCC. After phase 1a, tumor cohorts were expanded to 20 pts who will receive study treatment until confirmed disease progression or unacceptable toxicity (Phase 1b). The primary objective was to assess safety/tolerability of R in combination with D; preliminary efficacy will be examined in expansion cohorts. Results: As of the data cutoff on 27‐June‐16, a total of 20 ptswere treated in phase 1a; NSCLC andG/GEJDLT observation completed.NoDLT in NSCLC (6/6 pts evaluable); 1 DLT in G/GEJ (Grade [Gr] 3 proteinuria, serious adverse event [SAE]; 6/7 pts evaluable); HCCDLT observation ongoing (7 pts treated). Treatment‐emergent adverse events were reported for 19/20 pts, 10/20 pts experienced treatment‐related AEs (TRAEs). Except for the 1DLT, all other TRAEs wereGr 1/2 (abdominal pain [Gr 2 SAE], anorexia, arthromyalgia, asthenia, diarrhea [Gr 2 SAE], dysgeusia, eczema, thromboembolic event, fatigue, haematemesis [Gr 2 SAE], haematuria, headache, hypertension, infusion related reaction, nausea, proteinuria, pyrexia, rash, somnolence). 3 deaths were reported: two attributed to study disease (1 NSCLC and 1HCC); 1 attributed to AE not related to study treatment (HCC; respiratory failure). In addition, 1 G/GEJ pt in the phase 1a had confirmed partial response (cycle 2) after theDLT period, at the time of the data cutoff. Conclusions: The combination of D and R in NSCLC, G/GEJ, and HCC did not reveal any unexpected safety signals. As of 28‐June‐16, NSCLC and G/GEJ expansion cohorts were opened; HCC DLT observation was ongoing.