Crofelemer Misses Diarrhea End Point in Patients With Solid Tumors Receiving Targeted Therapy

Prophylaxis with crofelemer (Mytesi) did not lead to a statistically significant improvement in the incidence of diarrhea vs placebo in adult patients with solid tumors being treated with targeted therapy with or without chemotherapy, missing the primary end point of the phase 3 OnTARGET trial (NCT04538625).1

However, a subgroup analysis demonstrated that clinically relevant signals for crofelemer were reported in patients with breast and respiratory cancers, including lung cancer, which comprised more than 75% of patients enrolled on the study.

Jaguar Health, the developer of crofelemer, plans to confer with the FDA following a full review of the data. A complete analysis of the data will be presented in future presentations and publications.

“We believe the OnTARGET trial, designed boldly to address a broad array of [patients with] cancer undergoing therapy known to be associated with diarrhea, did not meet the primary end point given the heterogenous nature of the patients enrolled in the trial. Nevertheless, we are pleased that our preliminary analysis of the study data shows a clinically meaningful benefit in response to crofelemer in patients with breast and respiratory cancers, including lung cancer,” Lisa Conte, founder, president, and chief executive officer of Jaguar Health, stated in a news release.

“Breast and lung cancer are 2 of the top 3 most common cancer types, and treatment options for breast and lung cancer include the long-term use of targeted therapies that cause high incidences of diarrhea,” Conte continued. “We will continue to review data from prespecified and non-prespecified OnTARGET subgroups and then engage in discussions with the FDA to seek the most efficient pathway to bring crofelemer to these patients and address the important and debilitating [adverse] effect [AE] of cancer therapy–related diarrhea with the paradigm shifting mechanism of crofelemer. Patient dignity and the ability of patients to adhere with comfort to their cancer therapy is first and foremost in our ongoing development efforts."

Crofelemer was previously approved by the FDA for the symptomatic relief of diarrhea in adult patients with HIV/AIDS being treated with antiretroviral therapy.

OnTARGET was a multicenter, double-blind, placebo-controlled trial that enrolled 287 patients with 10 different types of solid tumors who were being treated with 24 different targeted therapies alone or in combination with chemotherapy.

To enroll in the study, patients were required to be at least 18 years of age with pathologically and/or radiologically confirmed solid tumors. They needed to be scheduled to receive targeted cancer therapy with a reported all-grade diarrhea rate of at least 50%. An ECOG performance status of 0 to 2 and a life expectancy of at least 12 weeks were required.²

Patients being treated with any type of immunotherapy were not allowed to participate, and patients could not receive any cancer therapy for which antidiarrheal prophylaxis was required. Other key exclusion criteria included ongoing irritable bowel syndrome or colitis; ongoing diarrhea or diarrheal episodes within 7 days of randomization; and laxative use within 7 days of enrollment.

Investigators randomly assigned patients to receive delayed-release crofelemer at 125 mg twice per day with or without food or matching placebo.

The study included a 12-week double-blind treatment phase, followed by a 12-week double-blind extension phase. Data from the extension phase have not yet been analyzed.¹

The frequency of loose or watery stools served as the trial’s primary end point. Secondary end points included the proportion of durable, clinical responders, the maximum number of loose or watery stools per week, and fecal incontinence.²

Regarding safety, crofelemer was well tolerated and generated an AE profile similar to the matching placebo. AEs were primarily related to anticancer therapy or the underlying disease.¹

References

1. Jaguar Health reports phase 3 OnTarget trial results for its cancer supportive care drug crofelemer. News release. Jaguar Health. July 23, 2024. Accessed July 23, 2024. https://jaguarhealth.gcs-web.com/news-releases/news-release-details/jaguar-health-reports-phase-3-ontarget-trial-results-its-0
2. Prophylaxis of diarrhea in adult cancer patients receiving targeted cancer therapy (OnTARGET). ClinicalTrials.gov. Updated April 15, 2024. Accessed July 23, 2024. https://clinicaltrials.gov/study/NCT04538625