On May 30, 2024 Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing development of targeted therapies for oncology, reported that it plans to initiate a Phase 3 clinical trial to evaluate gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- advanced breast cancer ("ABC") who are endocrine therapy resistant (Press release, Celcuity, MAY 30, 2024, View Source [SID1234643847]). In conjunction with its plan to conduct this study, Celcuity today entered into an amendment to an existing debt facility agreement and received an additional term loan of approximately $62 million.
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"There is an urgent need for better first-line treatment options for HR+/HER2- advanced breast cancer patients whose disease progressed while on or within 12 months of completing adjuvant endocrine for early breast cancer," said Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity. "We are very encouraged by the preliminary clinical data for gedatolisib as first-line treatment in patients with advanced breast cancer. In our Phase 1b trial that evaluated gedatolisib in combination with palbociclib and letrozole, median progression free survival was 48.6 months, and the ORR was 79%. These results highlighted the potential benefit of inhibiting the PI3K/AKT/mTOR pathway in treatment naïve patients."
Phase 3 VIKTORIA-2 Clinical Trial
The Phase 3 VIKTORIA-2 clinical trial will be an open-label, randomized study to evaluate the efficacy and safety of gedatolisib combined with fulvestrant plus a CDK4/6 inhibitor in comparison to fulvestrant plus a CDK4/6 inhibitor as first-line treatment for patients with HR+/HER2- ABC who are endocrine therapy resistant. For the CDK4/6 inhibitor, investigators may choose either ribociclib or palbociclib. The safety profile of gedatolisib combined with fulvestrant and palbociclib is well described, but the investigational combination of gedatolisib with ribociclib has not yet been clinically tested. Therefore, a safety run-in of approximately 12-36 subjects will evaluate the safety profile of gedatolisib combined with ribociclib and fulvestrant. The safety run-in will be completed, and gedatolisib’s Phase 3 dose confirmed, before enrolling patients in the Phase 3 portion of the study.
For the Phase 3 study, approximately 638 subjects who meet the eligibility criteria will be assigned to a cohort based on their PIK3CA mutation status. After the investigator selects the CDK4/6 inhibitor for a subject, the subject will then be randomly assigned on a 1:1 basis to either Arm A (gedatolisib, fulvestrant, and Investigator’s choice of ribociclib or palbociclib or Arm B (fulvestrant and Investigator’s choice of ribociclib or palbociclib).
The clinical trial primary endpoints are progression free survival (PFS), per RECIST 1.1 criteria, as assessed by blinded independent central review. The primary PFS endpoints will be evaluated separately in subjects who are PI3KCA wild type and PI3KCA mutant.
The study’s design was reviewed and discussed with the U.S. Food and Drug Administration (FDA) during a Type C meeting.
This global trial is expected to enroll subjects at up to 200 clinical sites across North America, Europe, Latin America, and Asia. Celcuity expects to enroll the first patient in the second quarter of 2025.
"We are excited to have secured the additional capital so we could accelerate initiation of our second Phase 3 study," said Brian Sullivan, CEO and co-founder of Celcuity. "Allowing investigators to choose between ribociclib or palbociclib as the CDK4/6 inhibitor for their patients, and separately randomizing patients according to their PIK3CA status, are important elements of the trial design. We are pleased that the FDA concurred with our approach."
Amended debt financing agreement with Innovatus Capital Partners, LLC and Oxford Finance LLC
Today, Celcuity also amended its existing debt financing agreement with an affiliate of Innovatus Capital Partners, LLC ("Innovatus") and added Oxford Finance LLC ("Oxford") as a new lender to provide Celcuity with up to $180 million in term loans, a $105 million increase from the current debt financing agreement. At the closing of this amendment to the debt financing agreement, Celcuity will receive $61.7 million and will have $100 million of total debt outstanding. Celcuity will be able to draw an additional tranche of $30 million and an additional tranche of $50 million upon achievement of certain clinical trial and regulatory milestones. The amended debt facility has a 36-month interest only period, which can be extended to a 48-month period if certain conditions are met. The loans will mature on the fifth anniversary of the amended agreement date. The loan agreement includes customary warrant coverage and is secured by all of Celcuity’s assets. Armentum Partners LLC acted as sole advisor to Celcuity on this transaction.