G1 Therapeutics’ cancer drug trilaciclib has failed to beat placebo against multiple efficacy measures in phase 2. Trilaciclib performed well against its neutropenia-related primary endpoints but fell short in terms of response rate, prompting investors to send G1's stock down 26%.
North Carolina-based G1 designed the phase 2 to assess whether short-acting intravenous CDK4/6 inhibitor trilaciclib could reduce the occurrence and duration of Grade 4 neutropenia—a condition defined by abnormally low levels of a type of white blood cell—in patients with second or third-line small cell lung cancer (SCLC). The trial hit its primary endpoints by showing that trilaciclib, when added to chemotherapy drug topotecan, is more effective than placebo at controlling neutropenia.
That primary endpoint success enabled G1 to paint the results as positive. However, investors looked past the neutropenia data and zeroed in on a line deep in G1’s statement about rates of objective responses and clinical benefit seen in the trial, as well as the progression-free survival.
Of the 26 patients in the placebo arm, six responded, resulting in an objective response rate (ORR) of 23.1%. In the trilaciclib arm, four of the 30 patients responded, giving an ORR of 13.3%. The clinical benefit rate and progression-free survival were almost identical across the two arms, coming in at around 60% and 4.2 months, respectively.
G1 thinks trilaciclib may improve overall survival (OS) by preserving immune system function during chemotherapy. But G1 is yet to generate the mature OS data needed to validate that idea, and trilaciclib’s performance against other measures of efficacy has been mixed. A metastatic triple-negative breast cancer trial recently linked use of trilaciclib to improved ORR, but an earlier study in first-line SCLC found it was numerically worse than placebo against the objective response yardstick.
Despite that, G1 Chief Medical Officer Raj Malik thinks the biotech has emerged from the midphase program with data to support the advance of trilaciclib.
“We now have four randomized phase 2 trials showing trilaciclib’s multi-lineage myelopreservation benefits. We plan to meet with U.S. and European regulatory authorities in 2019 to discuss the totality of trilaciclib data and pathways to approval,” Malik said in a statement.