FDA Grants Fast Track Designation to INX-315 in CCNE1-Amplified, Platinum-Resistant Ovarian Cancer

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The FDA has granted fast track designation to the novel CDK2 inhibitor INX-315 for the treatment of adult patients with CCNE1-amplified, platinum-resistant or refractory ovarian cancer.¹

“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 co-founder of Incyclix Bio, stated 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.”

INX-315 is a potent and selective small molecule inhibitor of CDK2.^1,2 Dysregulated CDK2 activity often occurs through the amplification of CCNE1, which is a known resistance mechanism to oral CDK4/6 inhibitors, or the overexpression of cyclin E1.² CCNE1 amplification occurs in a broad range of solid tumors as well as a subset of patients with high-grade serous ovarian cancer; these tumor types are associated with poor prognosis. CCNE1-amplification is also correlated with resistance to platinum-based chemotherapy, creating an area of high unmet need in patients with the most common type of ovarian cancer.¹

INX-315 is under investigation in the phase 1/2 INX-315-01 trial (NCT05735080) and has not yet been approved by the FDA.

Overview of INX-315-01

This first-in-human, open-label, dose-escalation, combination and dose-expansion trial was designed to evaluate the safety, tolerability, pharmacokinetics, and early efficacy of this agent in patients with recurrent advanced or metastatic cancer.² This includes patients with CDK4/6 inhibitor–resistant, estrogen receptor (ER)–positive HER2-negative breast cancer who or those with CCNE1-amplified solid tumors who progressed on standard-of-care treatment.³

The study is being conducted in 3 parts: part A is assessing oral INX-315 monotherapy and combination therapy with fulvestrant in a dose-escalation setting, part B is evaluating INX-315 monotherapy in a dose-expansion cohort for ovarian cancer, and part C will assess INX-315 in combination with abemaciclib (Verzenio) and fulvestrant (Faslodex) in patients with advanced or metastatic hormone receptor (HR)–positive/HER2-negative breast cancer.

Key eligibility criteria across all study parts include an age of 18 years or older, an ECOG performance status of 0 or 1, measurable disease per RECIST 1.1 criteria, and adequate hematologic, hepatic, and renal function. Eligible tumor types include ER-positive/HER2-negative breast cancer that has progressed on or after CDK4/6 inhibition, CCNE1-amplified platinum-resistant/refractory epithelial ovarian cancer, and other solid tumors with known CCNE1 amplification. Patients with prior exposure to CDK2 inhibitors, including multi-CDK inhibitors with CDK2 activity, will be excluded.

The study’s primary end points include safety and tolerability, the incidence of DLTs (part A), the determination of recommended doses for expansion (part A), overall response rate (part B), selection of the recommended phase 2 dose (part B), and the antitumor activity of INX-315 in combination with abemaciclib and fulvestrant (part C). Secondary objectives include the characterization of INX-315 pharmacokinetics and other efficacy end points.

INX-315 in Breast Cancer and Other Solid Tumors

Updated results from part A of INX-315-01 were presented at the 2024 San Antonio Breast Cancer Symposium and showed that INX-315 monotherapy demonstrated antitumor activity and was well tolerated.²

Among all response-evaluable patients in part A (n = 30/31), 10% achieved a partial response (PR) and 63% had stable disease (SD). In the ER-positive/HER2-negative breast cancer cohort, 10% and 50% of patients had a PR and SD, respectively. Corresponding rates for patients with CCNE1-amplified high-grade serous ovarian/fallopian cancer were 20% and 80%.

One dose-limiting toxicity necessitating dose reduction (grade 3 fatigue) was reported in this patient population at the 600 mg daily dose. There were no treatment discontinuations due to adverse effects (AEs). Treatment-related AEs (TRAEs) occurred in 83.9% of patients, the majority of which were grade 1/2; only 16% of patients experienced a grade 3 or greater TRAE. The most frequent treatment-related AEs were thrombocytopenia (48.4%), nausea (38.7%), neutropenia (38.7%), and diarrhea (29.0%)

Serious AEs (SAEs) occurred in 32.2% patients, and none were determined to be treatment related. No fatal AEs were reported, and no AEs led to treatment discontinuation

Evaluation of the 400 mg twice-daily dose level is ongoing. Based on these findings, the 600 mg dose was selected for further investigation in combination with fulvestrant as well as the monotherapy expansion in part B of the study.

References

1. Incyclix Bio granted U.S. FDA Fast Track Designation for INX-315 to treat CCNE1-amplified platinum-resistant/refractory ovarian cancer. News Release. Incyclix Bio. April 30, 2025. Accessed April 29 2025. https://incyclixbio.com/news_releases/incyclix-bio-granted-u-s-fda-fast-track-designation-for-inx-315-to-treat-ccne1-amplified-platinum-resistant-refractory-ovarian-cancer/
2. Tan A, Giordano A, Shannon C, et al. INX-315, an oral, potent and selective CDK2 inhibitor in patients with CDK4/6 inhibitor resistant ER+/HER2- breast cancer or CCNE1 amplified solid tumors. Presented at: 2024 San Antonio Breast Conference Symposium; December 10-13, 2024; San Antonio, TX. P4-10-16.
3. 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 January 7, 2025. Accessed April 26, 2025. https://clinicaltrials.gov/study/NCT04030559