AZ's immunotherapy combo fails in phase 3 lung cancer trial

AstraZeneca’s Imfinzi plus standard chemo improves overall survival in untreated extensive-stage small cell lung cancer – but a combination therapy involving another immunotherapy does not, according to phase 3 trial results.

AZ had been hoping that the combination of Imfinzi, a PD-L1 class drug, and the CTLA-4 class tremelimumab, plus standard chemo, would improve overall survival (OS) in this group of patients whose cancer has spread throughout the lung or to other parts of the body.

But top-line results from the phase 3 CASPIAN trial showed that an arm of the trial involving the Imfinzi and tremelimumab combination did not show a statistically significant improvement in OS.

The safety and tolerability for Imfinzi and tremelimumab were consistent with the known safety profiles of these medicines, AZ said in a statement summarising top-line findings.

Detailed trial results will be published at a forthcoming medical meeting.

Regulators in the US, EU and Japan are already reviewing Imfinzi combined with etoposide and either carboplatin or cisplatin in this indication on the basis of interim data gathered last year.

The FDA has granted a priority review – shortened from 10 months to six months – and is due to make a decision in this indication during the coming weeks.

CASPIAN is a randomised, open-label, multi-centre, global, phase 3 trial in the first line treatment of 805 patients with extensive-stage small cell lung cancer (ES-SCLC).

The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of tremelimumab, versus chemotherapy alone.

In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation.

The trial was conducted in more than 200 centres across 23 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms.

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

Immune-oncology is an increasingly competitive market, and while Imfinzi is well behind the market leader, Merck & Co’s Keytruda (pembrolizumab), it is an important drug for the UK pharma, generating nearly $1.5 billion in sales in 2019.

It is already approved in two indications – unresectable stage 3 non-small cell lung cancer and advanced bladder cancer.

Imfinzi is also being tested in other uses including prostate, triple negative breast cancer, and cervical cancer.