A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226 Academic Article uri icon

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abstract

  • This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) ± tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du ± Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design. Both weight-based and fixed dosing of Du and Tr were explored. Du was continued until progression. Tr dosing was finite (up to 6 doses) with increasing dose and/or frequency by DL. 136 patients were enrolled. The majority of drug-related adverse events (AEs) were ≤ grade 2 and attributable to chemotherapy. AEs considered related to immunotherapy were mainly ≤ grade 2; the most frequent (occurring ≥10 %) were colitis/diarrhea, skin, and thyroid dysfunction. Seven patients had DLTs including pneumonitis, myocarditis, diarrhea, encephalitis, motor neuropathy, and enterocolitis. There were 2 treatment-related deaths. Tr and Du exposures did not appear affected by chemotherapy. Among the 73 non-small cell lung cancer (NSCLC) patients treated, the objective response rate was 51 % (95 %CI = 38.7-62.6 %) with a median progression-free and overall survival of 6.5 months (95 % CI = 5.5-9.4 months) and 19.8 months (95 % CI = 14.8 months - not yet reached) respectively. Anti-tumour activity was observed across PD-L1 subtypes. Du 1500 mg q3w and Tr 75 mg q3wx5 can be safely combined with platinum-doublet chemotherapy. Efficacy among NSCLC patients appears comparable to results from other immunotherapy and chemotherapy combination trials. NCT02537418.

authors

  • Juergens, Rosalyn
  • Hao, Desiree
  • Ellis, Peter
  • Tu, Dongsheng
  • Mates, Mihaela
  • Kollmannsberger, Christian
  • Bradbury, Penelope A
  • Tehfe, Moustapha
  • Wheatley-Price, Paul
  • Robinson, Andrew
  • Bebb, Gwyn
  • Laskin, Janessa
  • Goffin, John
  • Hilton, John
  • Tomiak, Anna
  • Hotte, Sebastien
  • Goss, Glenwood D
  • Brown-Walker, Pamela
  • Sun, Xiaoqun
  • Tsao, Ming-Sound
  • Cabanero, Michael
  • Gauthier, Isabelle
  • Song, Xuyang
  • Dennis, Phillip A
  • Seymour, Lesley K
  • Smoragiewicz, Martin
  • Laurie, Scott A

publication date

  • May 2020