FDA Grants Orphan Drug Designation to CID-078 for SCLC

FDA

The FDA has granted orphan drug designation (ODD) to the investigational cyclin A/B RxL inhibitor CID-078 for the treatment of patients with small cell lung cancer (SCLC).1

In preclinical studies, cyclin A/B RxL inhibitors have generated single-agent tumor regressions in various in vivo models. CID-078 is currently being evaluated in a phase 1, first-in-human trial (NCT06577987) designed to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the agent in patients with advanced solid tumors, including SCLC.

“The orphan drug designation from the FDA underscores both the seriousness of SCLC and the lack of effective treatment options,” Michael C. Cox, PharmD, MHSc, BCOP, senior vice president and head of early development at Circle Pharma, stated in a news release. “We are committed to accelerating the clinical development of CID-078 to offer new hope for patients who face limited therapeutic choices.”

Dose-Escalation Design and Enrollment Criteria

Part 1a of the study is serving as dose escalation, utilizing a backfill Bayesian Optimal Interval design to determine the recommended dose for expansion (RDE).2 Part 1b is investigating a reformulated oral version of CID-078. Part 1a includes patients with locally advanced or metastatic solid tumors that have progressed or were not responsive to available therapies, and for whom no standard or available curative therapy exists. The backfill portion of part 1a included patients with SCLC, triple-negative breast cancer, and solid tumors harboring Rb1 alterations or loss of Rb protein function.

For parts 1a and 1b, patients must have measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1. Additionally, the patient must be at least 18 years of age with an estimated life expectancy greater than 12 weeks and the ability to swallow oral capsules. Where medically feasible, a fresh biopsy is preferred; if not possible, archival tumor tissue is acceptable, with enrollment also permissible on a case-by-case basis following sponsor discussion if no tissue is available. Adequate hematological, renal, and hepatic function is required.

Patients enrolling in the food effect cohort of part 1b must also be able to consume a standardized high-fat, high-calorie, or low-fat meal within 25 minutes, depending on cohort assignment.

Dose-Expansion Design and Enrollment Criteria

Part 2 will serve as dose expansion, and investigators will enroll patients with histologically or cytologically confirmed, advanced or metastatic solid tumors that have progressed on or were nonresponsive to prior standard therapies, with no remaining curative options. Specific cohorts will include TNBC, SCLC, and solid tumors with a documented Rb1 genomic alteration or loss of Rb protein function.

Patients must be 12 years of age, weigh at least 40 kg, and have measurable disease per RECIST 1.1 criteria. An ECOG performance status of 0 to 1 is needed for those older than 18 years of age; a Karnofsky score of greater than 70% is required for patients 16 to 18 years of age; and a Lansky performance status of at least 70% is needed for patients under 16 years of age.

During the study, CID-078 is being given twice per day in 21-day treatment cycles until disease progression or other discontinuation criteria are met.

Safety, the incidence of dose-limiting toxicities, and determining the recommended phase 2 dose are primary end points for part 1. In part 2, overall response rate, duration of response, and progression-free survival will be the primary end points.

References

1. Circle Pharma receives FDA orphan drug designation for CID-078 for the treatment of small cell lung cancer. News Release. Cricle Pharma. June 16, 2025. Accessed June 16, 2025. https://circlepharma.com/circle-pharma-receives-fda-orphan-drug-designation-for-cid-078-for-the-treatment-of-small-cell-lung-cancer
2. Safety/efficacy study of CID-078 in patients with advanced solid tumor malignancies. ClinicalTrials.gov. Updated May 23, 2025. Accessed June 16, 2025. https://clinicaltrials.gov/study/NCT06577987