Astra throws doubt on one oncology combo approach

This morning’s discontinuation of Astrazeneca’s lung cancer study combining oleclumab with AZD4635 should be of interest to Corvus and Novartis. The latter two companies are also pursuing combinations of in-house projects that have the same mechanisms of action: co-blocking CD73 and the A2A receptor. The two pathways are thought to be related, and there is some preclinical rationale behind blocking them both. Astra today stressed that it was continuing to work on combinations, and indeed a separate oleclumab/AZD4635 trial in prostate cancer is continuing. The group has also recently begun new studies combining oleclumab with Imfinzi, as well as with Innate Pharma’s anti-CD39 MAb IPH5201. Corvus’s A2A approach, once implied only in Parkinson’s disease, had earlier disappointed in combination with Tecentriq (AACR – Parkinson’s approach to cancer needs more work, Aptil 5, 2017). And yesterday the company disappointed further, falling 5% after the same combo posted just one partial remission among 35 subjects with very late-line prostate cancer, according to an abstract at Asco’s Genitourinary Cancers Symposium.

Selected anti-CD73 and A2A receptor inhibitor projects
Company CD73 A2A Combo work? Clinical study summary
Astrazeneca Oleclumab AZD4635* Yes Discontinued combo in EGFRm NSCLC
Corvus CPI-006 Ciforadenant Yes Phase I as monotherapies & combo (also with PD-1)
Arcus AB680 AB928 No Studies as monotherapies and in combo with PD-1 or Tigit
Novartis SRF373/ NZV930** PBF 509/ NIR178 Yes Phase I as monotherapies & combo (also with spartalizumab)
Bristol-Myers Squibb BMS-986179 (none) NA Phase I monotherapy & Opdivo combo
I-Mab/Tracon TJD5 (none) NA Phase I Tecentriq combo
Source: EvaluatePharma. *Licensed from Sosei; **licensed from Surface Oncology.

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