AstraZeneca’s Mystic OS analysis paints tremelimumab as a dud in NSCLC

AstraZeneca's Cambridge, U.K. R&D center. (AstraZeneca)

Overall survival data from AstraZeneca’s phase 3 Mystic trial have cast more doubts on the prospects of anti-CTLA4 antibody tremelimumab. The readout suggests that, if anything, adding tremelimumab to PD-L1 drug Imfinzi results in worse outcomes in metastatic non-small cell lung cancer (NSCLC).

In keeping with earlier Mystic readouts, the OS data features more black clouds than silver linings. The latest analysis shows how Imfinzi, with or without tremelimumab, performed against standard of care chemotherapy in previously untreated patients with metastatic NSCLC. At least 25% of cancer cells in the analyzed patient population expressed PD-L1.

Neither Imfinzi nor Imfinzi plus tremelimumab delivered statistically better OS than platinum-based chemotherapy, the standard of care comparator. To compound matters, the OS data raise questions about whether tremelimumab is hindering, not helping.

AstraZeneca pointed to a hazard ratio of 0.76 in the Imfinzi monotherapy arm as a cause for a degree of optimism. That suggests Imfinzi may be better than standard of care. But the difference was too small to hit statistical significance—the p value was 0.036—and the confidence interval is too broad to rule out that Imfinzi is no better than chemotherapy.

That was the positive part of the analysis. The picture darkens once tremelimumab is involved. When the CTLA-4 drug was added to Imfinzi, the HR came in at 0.85, suggesting patients may have lived longer if they received the PD-L1 inhibitor as a monotherapy.

AstraZeneca saw Mystic as a way to leapfrog its rivals and establish Imfinzi plus tremelimumab as a first-line treatment in NSCLC. The delivery of progression-free survival data last year put a big dent in that plan. And the inability of either of AstraZeneca’s regimens to extend overall survival has dealt it another big blow.

Research is continuing, though. AstraZeneca thinks the OS data justify further analysis in exploratory subgroups, although the available evidence leaves little scope for optimism about tremelimumab.

Elsewhere, AstraZeneca is continuing to test Imfinzi in combination with tremelimumab in two other phase 3 first-line NSCLC trials, dubbed Neptune and Poseidon.