Adverse Survival Signal Leads G1 to Stop Pivotal Test in Colorectal Cancer

G1 Therapeutics’ approach to cancer does not kill tumors. Instead, the biotech’s drug, trilaciclib, protects bone marrow from the damaging effects of chemotherapy, reducing the duration and severity of the problems that can limit the use of this cancer treatment. Since trilaciclib’s initial approval in
small cell lung cancer, G1 has pursued more clinical trials that could support expanding the drug to other cancers. Colorectal cancer will no longer be one of them.

On Monday, G1 reported preliminary data showing that the placebo group outperformed the trilaciclib arm in helping patients live longer. G1 said it has decided to stop the colorectal cancer trial. The Research Triangle Park, North Carolina-based company added that the independent data monitoring committee reached the same conclusion on its own.

The Phase 3 study enrolled 325 patients whose colorectal cancer had metastasized. In order to provide its protective effects, intravenously infused trilaciclib is administered prior to chemotherapy. Study participants were randomly assigned to receive the G1 drug or a placebo; they were then given chemotherapy plus Avastin, a Roche drug approved as a second-line colorectal cancer treatment. This regimen was followed for two consecutive days of every 14-day treatment cycle. Patients received up to 12 cycles followed by maintenance therapy.

G1 said the results showed the trilaciclib arm met the main goal of reducing severe neutropenia, which is an abnormally low level of a type of white blood cell called a neutrophil. Treatment with the G1 drug also led to a clinically meaningful reduction of chemotherapy-induced diarrhea compared to placebo.

However, the company also said that the early efficacy data, including overall response rate and preliminary measures of how long patients are living while receiving treatment, favored the placebo group. This adverse survival signal was not reported in earlier tests of the drug in small cell lung cancer and triple negative breast cancer. G1 said more details from the Phase 3 results in colorectal cancer will be presented at an upcoming scientific meeting and submitted for publication.

“All of us at G1 are disappointed in this surprising outcome for patients with [colorectal cancer], but we remain committed to the potential of trilaciclib to impact the lives of many cancer patients in other indications,” G1’s CEO Jack Bailey said in a prepared statement. “We are increasingly encouraged by the real-world performance of trilaciclib in patients with extensive-stage small cell lung cancer and look forward to upcoming readouts in our other ongoing trials.”

Trilaciclib won its small cell lung cancer approval in 2021. G1 markets the drug under the name “Cosela.” Last year, the drug accounted for $22.5 million in sales through the third quarter. The company has been counting on landing additional approvals in other indications as a way of growing revenue. G1 has said a Phase 3 study in triple negative breast cancer is expected to report initial data in the second half of 2023; a Phase 2 test of trilaciclib in bladder cancer has completed enrollment.

Image by the National Cancer Institute