Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Phase 1b study of the safety and antitumour activity of durvalumab (MEDI4736) + tremelimumab in advanced NSCLC

Date

19 Dec 2015

Session

Thoracic cancers

Presenters

Naiyer Rizvi

Citation

Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532

Authors

N. Rizvi1, A. Balmanoukian2, S.B. Goldberg3, J. Chaft4, R.E. Sanborn5, M.C. Rebelatto6, R. Narwal7, P.B. Robbins6, Y. Gu8, J.J. Karakunnel9, S. Antonia10

Author affiliations

  • 1 Department Of Medicine, Columbia University Hospital, 10032 - New York/US
  • 2 Department Of Hematology/oncology, The Angeles Clinic and Research Institute, Los Angeles/US
  • 3 Yale Cancer Center, Yale University, New Haven/US
  • 4 Department Of Medicine, Memorial Sloan Kettering Cancer Center, New York/US
  • 5 Thoracic Oncology, Earle A. Chiles Research Institute, Providence Cancer Center, Portland/US
  • 6 Translational Medicine, MedImmune, Gaithersburg/US
  • 7 Clinical Pharmacology And Dmpk, MedImmune, Gaithersburg/US
  • 8 Biostatistics, MedImmune, Gaithersburg/US
  • 9 Clinical Development, MedImmune, Gaithersburg/US
  • 10 Medical Oncology, H Lee Moffitt Cancer Center, Tampa/US
More

Aim/Background

Durvalumab (D; MEDI4736), a human IgG1 anti-PD-L1 antibody, and tremelimumab (T), a human IgG2 anti-CTLA-4 antibody, have shown acceptable safety profiles and antitumour activity as monotherapies; preclinical data suggest their combination may have greater antitumour activity vs either agent alone.

Methods

This is a phase 1 open-label dose-escalation/expansion study (NCT02000947) of D + T in patients (pts) with Stage III/IV NSCLC (≤3 prior therapies; immunotherapy naïve). Primary endpoint is safety and tolerability; dose-limiting toxicity (DLT) period is 28 days. Secondary endpoints include RECIST v1.1 response. PD-L1 expression was tested retrospectively.

Results

As of 15 Apr 2015, 102 pts have received D + T in the dose-escalation phase (Table).

D Q4W + T Q4W D Q2W + T Q4W
Cohort 1a 2a 3a 3b 4 4a 5 5a 8 9
Dose D (mg/kg) + T (mg/kg) 3 + 1 10 + 1 15 + 1 10 + 3 20 + 1 15 + 3 15 + 10 20 + 3 10 + 1 10 + 3
n 3 3 18 3 18 14 9 6 17 11
Pts with ≥1 drug-related AE, n
All grades 1 3 11 3 9 12 8 5 12 10
Grade 3/4 0 2 7 2 4 6 7 5 3 5
Drug-related discontinuations 0 1 2 2 1 4 4 3 0 3
Drug-related deaths 0 1 0 0 0 0 0 1 0 0

2 pts in Cohort 5a had a DLT (Grade [G] 3 increased AST/ALT, G4 increased lipase). 73% had ≥1 drug-related AE; most frequent were diarrhoea (27%) and fatigue (23%). 40% had ≥1 G3/4 related AE; most frequent were colitis (9%) and diarrhoea (8%). 20% had drug-related AEs leading to discontinuation; most frequent was colitis (7%). 2 drug-related AEs led to death. AEs were manageable with standard therapy, except G4 myasthenia gravis and G5 polymyositis (n = 1, Cohort 2a) and G5 neuromuscular disorder (n = 1, Cohort 5a). Increasing T doses with fixed D dose were associated with greater frequency of AEs without deeper, earlier or greater number of responses. D + T had dose-proportional PK exposures in line with monotherapy studies. Of 63 efficacy evaluable pts dosed ≥16 weeks before cutoff, 17 (27%) had partial responses (PR; confirmed/unconfirmed); 14 (22%) had stable disease. PRs occurred in 6 of 18 pts (33%) with PD-L1+ tumours, 9 of 33 pts (27%) with PD-L1 tumours.

Conclusions

M + T has a manageable safety profile and evidence of clinical activity in advanced NSCLC, including PD-L1 disease, supporting continued study of the combination. Recruitment is ongoing.

Clinical trial identification

NCT02000947

Disclosure

N. Rizvi: consulting income from MedImmune, Roche, Merck, AstraZeneca and BMS. A. Balmanoukian: Corporate-sponsored research MedImmune, Merck, Genentech, Merck Serono, Pfizer, BMS; other substantive relationships speakers Bureau for Bristol Myers Squibb. S.B. Goldberg: Advisory Board: Clovis, Boehringer Ingelheim Corporate-Sponsored Research: AstraZeneca, Clovis, Genentech, Merck, Immunogen, Kadmon. J. Chaft: Advisory Board: Genentech, Myriad, Biodesix. R.E. Sanborn: no personal financial conflicts of interest, but institution receives research support from Medimmune. M.C. Rebelatto, R. Narwal, P.B. Robbins, Y. Gu, J.J. Karakunnel: employee of MedImmune and owns stock/stock options in AstraZeneca. S. Antonia: Advisory board: Merck Corporate sponsored research; consultant for BMS, MedImmune/AstraZeneca.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings