- A closely watched drug combination of AstraZeneca plc's immunotherapies Imfinzi and tremelimumab fell short of its goal in a Phase 3 study of previously treated lung cancer patients, likely narrowing the regimen's future potential and raising the stakes for a key trial readout later this year.
- Importantly, though, AstraZeneca's study primarily tested the immunotherapy combination against chemotherapy in patients whose tumors expressed low or negative levels of the PD-L1 protein — a group typically less likely to respond to checkpoint inhibitors like Imfinzi.
- The British pharma also said results from the study suggested Imfinzi monotherapy reduced the risk of death versus chemotherapy in PD-L1 high patients. That result, however, was not statistically significant as AstraZeneca hadn't sufficiently powered the study to test that comparison.
The negative results from AstraZeneca's study, called ARCTIC, continue the British pharma's up-and-down performance in lung cancer drug development. Past setbacks in metastatic disease have been followed by successes in earlier-stage and smaller subsets of lung cancer.
Just last week, for example, another drug called Tagrisso (osimertinib) secured an important U.S. approval for first-line treatment of advanced non-small cell lung cancer (NSCLC) in patients who test positive for EGFR mutations.
Analyst and investor expectations were not high for ARCTIC given the prior failure of Imfinzi (durvalumab) and tremelimumab to extend progression-free survival (PFS) in first-line treatment of NSCLC. Still, the results underscore the limits to the potential of AstraZeneca's combination.
According to the company, Imfinzi plus tremelimumab given as a third-line therapy failed to deliver a statistically significant benefit over chemotherapy on either PFS or overall survival in PD-L1 low patients.
Although this patient population is generally considered less responsive to immunotherapy, Bristol-Myers Squibb Company recently showed certain PD-L1 low patients with high scores on another biomarker measure could still benefit from combination immunotherapy.
One possible silver lining for AstraZeneca, however, is the positive signal from Imfinzi monotherapy, which could augur well for future success in PD-L1 high patients.
The real test for the Imfinzi/tremelimumab combination will come in the second half of this year, when survival data from the MYSTIC study in first-line NSCLC is expected. Interim results released last July showed the combo failed to extend PFS, dealing a major blow to AstraZeneca's chances of competing with market leaders Merck & Co. and Bristol-Myers in metastatic disease.
An OS win is still possible, which would put AstraZeneca in the mix to compete in combination immunotherapy.
Imfinzi's commercial potential in lung cancer, however, is likely to stem mostly from its approval for Stage 3, unresectable tumors. In that setting, AstraZeneca estimates it is two or more years ahead of its rivals, forecasting annual sales to eventually crest $1 billion from that indication alone.
Two other studies testing Imfinzi plus tremelimumab in head and neck cancer, as well as another in first-line lung cancer, are expected to deliver results this year as well.