2O - Phase 1 study of ramucirumab (R) plus durvalumab (D) in patients (pts) with locally advanced and unresectable or metastatic gastrointestinal or tho...

Date 04 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Proffered paper session
Presenter Chia-Chi Lin
Citation Annals of Oncology (2016) 27 (suppl_8): viii1-viii2. 10.1093/annonc/mdw525
Authors C. Lin1, T. Golan2, J. Corral3, V. Moreno4, H.C. Chung5, H. Wasserstrom6, J. Yang6, G. Mi7, Y. Bang8
  • 1Oncology, National Taiwan University Hospital, 10002 - Taipei/TW
  • 2Oncology, Oncology Institute Sheba Medical Center, Tel Hashomer/IL
  • 3Oncology, Virgen del Rocio University Hospital, Seville/ES
  • 4Oncology, START MADRID-FJD, Hospital Fundación, Madrid/ES
  • 5Department Of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul/KR
  • 6Global Medical Sciences, Eli Lilly and Company, Bridgewater/US
  • 7Global Statisical Sciences, Eli Lilly and Company, Indianapolis/US
  • 8Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR

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 pts were treated in phase 1a; NSCLC and G/GEJ DLT observation completed. No DLT in NSCLC (6/6 pts evaluable); 1 DLT in G/GEJ (Grade [Gr] 3 proteinuria, serious adverse event [SAE]; 6/7 pts evaluable); HCC DLT 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 1 DLT, all other TRAEs were Gr 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 1 HCC); 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 the DLT 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.

Clinical trial identification

ClinicalTrials.gov Identifier: NCT02572687

Legal entity responsible for the study

Eli Lilly and Company

Funding

Eli Lilly and Company

Disclosure

H.C. Chung: Research support: Eli Lilly and Company, GSK, MSD Speakers Bureau: Merck-Serono, Eli Lilly and Company Consultation: Taiho, Celltrion, MSD, Eli Lilly and Company, BMS, Quintiles. H. Wasserstrom, J. Yang, G. Mi: Employee of Eli Lilly and Company and holds equity in the company. Y-J. Bang: Research funding (to the institution) and consulting role with both Lilly and AstraZeneca. All other authors have declared no conflicts of interest.