CRAIN Trial Completes, ICMR Develops Pill: Two New Approaches for Cervical Cancer
Two novel cervical cancer treatment approaches show progress: the CRAIN trial has completed dose-finding for tolinapant, an apoptosis inhibitor, while ICMR develops the SHetA2 pill for precancerous lesions.
Progress against cervical cancer is advancing on two fronts: a UK-led clinical trial has completed testing a drug that reactivates cell death mechanisms in tumor cells, and a pill under development in India aims to stop precancerous lesions from progressing to full-blown disease.
The CRAIN trial, delivered by the Southampton Clinical Trials Unit and led nationally from the University of Manchester, tested tolinapant — an Inhibitor of Apoptosis Proteins (IAP) — alongside standard chemoradiotherapy. Chemoradiotherapy remains an effective standard treatment but causes significant long-term side effects, and around half of patients see their cancer return. Tolinapant is designed to switch apoptosis back on within cancer cells, and laboratory studies showed it increases cancer cell kill when added to chemoradiotherapy. The trial successfully investigated escalating doses to determine the maximum tolerated dose and a recommended dose for future Phase II studies. Data collection is finished and results are undergoing final analysis ahead of publication later this year.
Biological samples collected during the trial are now being examined by experts at the Manchester Cancer Research Centre to understand how tolinapant behaves inside the body, how it interacts with radiotherapy and chemotherapy, and which biological markers could predict treatment response. These insights may help identify which patients are most likely to benefit from adding tolinapant to their treatment programme.
Findings from CRAIN will inform whether a larger Phase II trial should proceed. That next step would examine whether combining tolinapant with standard chemoradiotherapy can destroy more cancer cells, reduce the likelihood of recurrence, lessen long-term side effects, and improve overall survival.
Separately, the Indian Council of Medical Research (ICMR) has developed SHetA2, a pill that could stop human papillomavirus (HPV) from causing cervical cancer. If future clinical trials establish its effectiveness, it could become one of the first targeted drug therapies to treat cervical intraepithelial neoplasia (CIN), the precancerous condition that precedes cervical cancer, without requiring surgery.