The FDA granted a fast track designation to INX-315 (Incyclix Bio, LLC) for the treatment of cyclin E1 (CCNE1)-amplified platinum-resistant or -refractory ovarian cancer. Preclinical data demonstrated that in CCNE1-amplified cancer models, INX-315 was able to potently block Rb phosphorylation, arrest cells in the G1 phase of the cell cycle, and inhibit cell proliferation. It also demonstrated robust single-agent in vivo activity.1,2
What Does a Fast Track Designation Mean?
Fast track is a process designed to facilitate the development and expedite the review of drugs needed to treat serious conditions, filling an unmet medical need—essentially, bringing drugs of high need to a patient earlier. Fast track addresses a range of serious conditions. A fast track drug must show some advantage over currently available therapies, such as the following: superior effectiveness or an improved effect on serious outcomes; avoidance of serious side effects of available therapies; improves diagnosis of a serious condition in which early diagnosis results in an improved outcome; decreased clinically significant toxicity of available therapies that is common, causing discontinuation of treatment; and the ability to address emerging or anticipated public health needs.
Ovarian cancer is considered to be the deadliest gynecologic malignancy. In the frontline setting, patients are treated with a platinum and taxane doublet. Although approximately 40% to 60% of patients achieve a complete clinical response with this line of chemotherapy, approximately 25% of patients have disease that is platinum-resistant or -refractory, with a median overall survival of approximately 1 year.2 The amplification of CCNE1 and cyclin E2 occurs in a broad range of solid tumors and in a significant group of patients with high-grade serous ovarian cancer (HGSOC). Additionally, CCNE1 amplification is also associated with resistance to platinum-based chemotherapy, creating a significant area of unmet need in patients with the most common type of ovarian cancer.1,3
INX-315 is a novel, potent, and selective CDK2 inhibitor that is currently undergoing evaluation in the ongoing first-in-human phase 1/2 clinical trial, INX-315-01 (NCT05735080)4 to evaluate its safety, tolerability, pharmacokinetics, and preliminary antitumor activity in patients with recurrent advanced/metastatic cancer. The study will be conducted in 3 parts: part A, which consists of an oral INX-315 monotherapy dose escalation and combination therapy with fulvestrant (Faslodex; AstraZeneca); part B, an ovarian cancer INX-315 monotherapy dose expansion; and part C, an INX-315 combination therapy with abemaciclib (Verzenio; Eli Lilly and Co) and fulvestrant in advanced/metastatic breast cancer (dose escalation and expansion).1,4
Part B will expand to at least 2 dose levels determined by the SMC, according to the investigators. Patients with platinum-refractory or platinum-resistant advanced or metastatic ovarian cancer with CCNE1 amplifications will be enrolled. Additionally, part B will open for enrollment once the SMC has selected the dose levels to be evaluated from the part A portion of the study. Patients from part A are not permitted to rejoin or continue the study in part B. Approximately 30 patients will be randomly assigned to receive 1 of the dose levels of INX-315.4
About the Trial
Trial Name: Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer (INX-315-01)
ClinicalTrials.gov ID: NCT05735080
Sponsor: Incyclix Bio
Completion Date (Estimated): June 2026
The primary outcomes for part B are the incidence of treatment-emergent adverse events (AEs), which will be assessed up to 12 months, as well as overall response rate and selection of recommended phase 2 dose, both of which will be assessed up to 36 months.4
“The FDA’s decision to grant fast track designation for INX-315 reflects the best-in-class potential of our CDK2 inhibitor, the strength of our preclinical and early clinical data and the urgency to address significant unmet need in patients with CCNE1-amplified platinum-resistant/refractory ovarian cancer,” Patrick Roberts, PharmD, PhD, CEO and cofounder of Incyclix Bio, said in a news release. “We look forward to working closely with the FDA to advance the clinical development of INX-315 to bring it to patients as soon as possible.”1
REFERENCES
2. Trub AG, Bisi JE, Dietrich C, et al. INX-315, a potent and selective CDK2 inhibitor, demonstrates robust antitumor activity in CCNE1-amplified cancers. Accessed April 29, 2025. https://incyclixbio.com/wp-content/uploads/2023/04/AACR-2023.pdf
3. Gorski JW, Ueland FR, Kolesar JM. CCNE1 amplification as a predictive biomarker of chemotherapy resistance in epithelial ovarian cancer. Diagnostics (Basel). 2020;10(5):279. doi:10.3390/diagnostics10050279
4. Open-label study to evaluate the safety, tolerability, PK, and efficacy of INX-315 in patients with advanced cancer (INX-315-01). ClinicalTrials.gov. Updated April 27, 2025. Accessed April 29, 2025. https://www.clinicaltrials.gov/study/NCT05735080
