On August 5, Mologen AG announced top-line data from the pivotal Phase III IMPALA trial.

The study showed maintenance lefitolimod monotherapy did not improve overall survival when compared against the local standard of care in patients with metastatic colorectal cancer (CRC).

This readout has caused disappointment for the company and its investors as they were aware that if successful, it could have become a practice-changing additional treatment.

Metastatic colorectal cancer treatment

IMPALA is the second Mologen AG Phase III maintenance trial in which lefitolimod has been unable to show improved clinical efficacy. In the post-trial analysis, clinicians highlighted that in both the IMPALA and IMPACT trials, the drug had a favourable safety profile and hence has the potential to be used in combination therapy.

This key finding has shaped the future direction for the drug as Mologen AG has confirmed that it will only pursue combination studies. At present, the company has a Phase I/II trial testing the drug as a melanoma therapy in combination with the checkpoint inhibitor ipilimumab, and hopes this combination strategy will result in improved clinical efficacy; however, no data have been published as yet.

In the future, it will become increasingly difficult for drug companies to enter this line of therapy in CRC, as it is dominated by capecitabine or other chemotherapy and Roche’s Avastin, which had positive trial readouts in 2015.

Furthermore, as Avastin is due to face biosimilar erosion starting in 2020, both regimens will be deemed to be more cost-effective in comparison to branded maintenance therapies.

Therefore, drug companies need to look to optimise maintenance treatments for patients in specific subgroups, such as biomarker-defined populations or those with stable disease post-first-line therapy. These are still areas of unmet need as CRC patients with complete remission or partial remission after induction therapy benefitted more from current maintenance treatment options than patients with stable disease.

Forthcoming reports

GlobalData (2019). Colorectal Cancer: Global Drug Forecast and Market Analysis to 2028, to be published