AstraZeneca's cancer checkpoint combo looks promising in small lung cancer study

AstraZeneca CEO Pascal Soriot

AstraZeneca ($AZN) has successfully wrapped a small proof-of-concept study to help demonstrate how two immunotherapy drugs will likely work better than one. The pharma giant is reporting that a combination of the PD-L1 drug durvalumab combined with the CTLA-4 treatment tremelimumab achieved an objective tumor response rate of 23% for metastatic non-small cell lung cancer patients.

Significantly, investigators were able to track similar response rates across both PD-L1 positive and negative patient groups in the combo study, which helps heighten expectations for these programs, now in late-stage development.

"The latest findings reinforce our belief that the combination strategy we are pursuing is key to the future success of immuno-oncology treatment," said Medimmune oncology chief Ed Bradley.

By hitting the checkpoint receptor PD-L1, durvalumab is designed to break links with PD-1 and B7.1, helping to unleash a T cell attack on cancer cells. Tremelimumab works on a different target, inhibiting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) in a separate booster for the immune response. 

Both drugs feature prominently in AstraZeneca's case that it can make a comeback with the help of new cancer drugs. CEO Pascal Soriot has promised investors annual revenue north of $45 billion in 2023, and that will depend heavily on the market success of these drugs. But durvalumab has lost some of its glitter as Merck ($MRK) and Bristol-Myers Squibb ($BMY) won the advantage of being first to market. And Roche ($RHHBY) has been in hot pursuit of a near-term launch of atezolizumab, a PD-L1 rival to durvalumab, which has been steadily losing ground to the competition.

All the biopharma companies in the field are advancing new and better combos in the race to grab a share of what's expected to be a megablockbuster market.

"Combination therapy with durvalumab and tremelimumab demonstrated antitumor activity in patients with NSCLC regardless of PD-L1 status, including in patients with no evidence of tumor cell membrane PD-L1 staining," noted Scott Antonia from the Moffitt Cancer Center in Tampa. "The results suggest that this combination has potential as a treatment option for patients with PD-L1 negative tumors whose needs are not addressed by currently available therapies, including immunotherapies."

Not surprisingly for an advanced group of patients, there were considerable side effects to report on. Close to one in three of the patients in the study experienced a grade 3/4 adverse event, with 16% dropping out of the trial.

The Phase Ib results were published in The Lancet Oncology.

- here's the release

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