INX-315 Receives FDA Fast Track Status for CCNE1-Amplified Ovarian Cancer

INX-315 is being evaluated in multiple settings in the INX-315-01 trial.

The FDA has granted fast track designation to the novel, potent, selective CDK2 inhibitor INX-315 for the treatment of patients with CCNE1-amplified platinum-resistant/refractory ovarian cancer, per a news release from the developer of the drug, Incyclix Bio, LLC.¹

The safety, tolerability, preliminary antitumor activity, and pharmacokinetics of the CDK2 inhibitor in patients with recurrent advanced/metastatic cancer is being investigated in the first-in-human phase 1/2 INX-315-01 trial (NCT05735080).

“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,” said Partick Roberts, PharmD, PhD, chief executive officer and co-founder of Incyclix Bio, LLC in the press release.

INX-315-01 will investigate the use of INX-315 in both ovarian cancer and hormone receptor (HR)-positive, HER2-negative breast cancer that has progressed on standard-of-care treatment.²

The trial will be conducted in 3 parts: INX-315 monotherapy dose escalation and combination therapy with fulvestrant (Faslodex) (part A), ovarian cancer INX-315 monotherapy dose expansion (part B), and INX-315 plus abemaciclib (Verzenio) and fulvestrant (Faslodex) in advanced/metastatic breast cancer with dose escalation and expansion (part C).

“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,” remarked Roberts in the release.

The estimated date of primary completion is December 2025, with an estimated date of study completion of June 2026.²

Interim Analysis

Part A of the trial was used to assess safety, tolerability, and pharmacokinetics of single-agent INX-315 via dose escalation using the Bayesion optimal interval design. According to a press release from Incylclix Bio, LLC, interim data from part A revealed that among the 31 patients enrolled, single-agent INX-315 was safe and well-tolerated.³ One dose-limiting toxicity occurred (grade 3 fatigue), and no discontinuations due to severe adverse events or fatal AEs occurred.⁴

The treatment displayed antitumor activity in “heavily pretreated patients” with both breast and ovarian cancer. Among all patients on part A of the trial, 3 patients (10%) had a partial response (PR) and 19 (63%) had stable disease (SD). Two patients (20%) with ovarian cancer showed PR, and 8 (80%) showed SD. In those with breast cancer, 1 (10%) displayed PR, and 5 (50%) displayed SD.

Preliminary Safety Data

According to data presented in a poster at the San Antonio Breast Cancer Symposium, most treatment-related AEs (TRAEs) were grade 1 or 2, and TRAEs grade 3 or higher occurred in 16.1% of patients.⁴ TRAEs of any grade occurred 26 patients (83.9%).

The most common TRAEs were thrombocytopenia (48.4%), nausea (38.7%), neutropenia (38.7%), diarrhea (38.7), anemia (22.6), vomiting (19.4%), fatigue (16.1%), and leukopenia (16.1%). Although serious AEs were reported in 10 patients (32.2%), they were not deemed to be related to treatment with NIX-315.

The dosage of INX-315 selected by the safety committee for combination with fulvestrant and monotherapy expansion in part B is 600 mg once daily. A dosage of 400 mg of NIX-315 taken twice daily is still under investigation.

Patient Characteristics

In part A, the median age of enrolled patients was 60 (range, 29-78), and 74% of patients were female. The median number of previous lines of therapy was 4 (range, 1-9).^3,4 Nineteen patients (61%) had an ECOG status of 0, and 12 (39%) had an ECOG score of 1.

All patients with breast cancer enrolled in part A had received prior treatment with a CDK4/6 inhibitor, and 9 (90%) had received previous fulvestrant.

References

1. Incyclix Bio Granted U.S. FDA fast track designation for INX-315 to Tteat CCNE1-amplified platinum-resistant/refractory ovarian cancer. Inclyclix Bio, LLC. Published April 29, 2025. Accessed April 29, 2025. https://www.globenewswire.com/news-release/2025/04/29/3070088/0/en/Incyclix-Bio-Granted-U-S-FDA-Fast-Track-Designation-for-INX-315-to-Treat-CCNE1-Amplified-Platinum-Resistant-Refractory-Ovarian-Cancer.html
2. Open-label study to evaluate the safety, tolerability, PK, and efficacy of INX-315 in patients with advanced cancer (INX-315-01). ClinicalTrials.gov. Published February 21, 2021. Updated April 27, 2025. Accessed April 30, 2025. https://clinicaltrials.gov/study/NCT05735080?id=NCT05735080&rank=1
3. Incyclix Bio announces interim clinical data from the phase 1/2 clinical trial of INX-315 in patients with CDK4/6 inhibitor resistant ER+/HER2- breast cancer or CCNE1-amplified solid tumors. Incyclix Bio, LLC. Published December 13, 2024. Accessed April 30, 2025. https://incyclixbio.com/news_releases/incyclix-bio-announces-interim-clinical-data-from-the-phase-1-2-clinical-trial-of-inx-315-in-patients-with-cdk4-6-inhibitor-resistant-er-her2-breast-cancer-or-ccne1-amplified-solid-tumors/
4. Tan AR, Giordano A, Shannon C. INX-315, an oral, potent and selective CDK4/6 inhibitor resistant ER+/HER2-breast cancer or CCNE1 amplified solid tumors. Presented at: San Antonio Breast Cancer Symposium; December 10-13, 2024. Abstract P4-10-16.