Cosela/Immunochemotherapy Trial for Colorectal Cancer Stopped for Limited Anti-Tumor Efficacy Data


The PRESERVE 1 trial was discontinued due to responses and survival measures favoring placebo versus Cosela when added to a chemoimmunotherapy regimen.

G1 Therapeutics announced that it will terminate the phase 3 PRESERVE 1 trial assessing the addition of Cosela (trilaciclib) to FOLFOXIRI and Avastin (bevacizumab) for the treatment of metastatic colorectal cancer based on data demonstrating limited responses and improved survival measures.

In particular, the phase 3 PRESERVE 1 trial was discontinued because of its early antitumor efficacy data including overall response rate (patients who had a partial or complete response to therapy) and preliminary survival measures favored patients assigned placebo versus Cosela, according to a press release from G1 Therapeutics. The company noted that other trials adding Cosela to different chemotherapies did not demonstrate these findings in cancer types including triple-negative breast cancer and extensive-stage small cell lung cancer.

“Unfortunately, despite the robust myeloprotection and improved tolerability, early survival indicators, including the observed overall response rate in this trial, favor patients receiving placebo,” Malik said in the release. “These results in PRESERVE 1 are inconsistent with what we’ve observed in other tumors with different chemotherapy backbones. As a result of these topline results, we have made the decision to terminate this study.”

The PRESERVE 1 trial included 326 patients with metastatic colorectal cancer receiving first-line Cosela (the first treatment given for the disease as part of a set of treatments) or placebo in addition to triplet therapy with FOLFOXIRI (fluorouracil, folinic acid, oxaliplatin and irinotecan) and Avastin.

Patients assigned Cosela did not have improvements in overall response rates (50% versus 61%) compared with placebo. Given these results, the researchers determined that the likelihood that patients assigned Cosela would achieve progression-free survival (the time during and after treatment when a patient with cancer lives with the disease without worsening) and overall survival (the time from diagnosis or treatment initiation when a patient with cancer is still alive).

The announcement to terminate the trial was made despite its initial results, which demonstrated significant reductions in the occurrence of severe neutropenia (an abnormally low white blood cell count) during the administration of Cosela. Severe neutropenia occurred less often in patients assigned Cosela compared with placebo (1% versus 20%), and the duration of neutropenia during the first four treatment cycles was shorter in the Cosela group (0.1 days versus 1.3 days), according to the release.

“PRESERVE 1 is the first clinical trial evaluation of (Cosela) in a (fluorouracil)-based chemotherapeutic backbone,” said Dr. Raj Malik, chief medical officer of G1 Therapeutics, in the release. “This study reaffirms that (Cosela) is a highly effective drug for myeloprotection that all but eliminated neutropenia as a concern for patients with (colorectal cancer) in the trial, which helps inform our ongoing combination studies with other highly myelotoxic regimens like (antibody drug conjugates).”

Cosela also reduced the rate of chemotherapy-induced diarrhea compared with placebo, and contributed to fewer chemotherapy dose reductions and delays, according to the release.

“We are increasingly encouraged by the real-world performance of (Cosela) in patients with extensive stage small cell lung cancer and look forward to upcoming readouts in our other ongoing trials,” said Jack Bailey, chief executive officer of G1 Therapeutics, in the release.

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