Abstract CT023: Early clinical activity from the phase 1 evaluation of CID-078, a novel Cyclin A/B-RxL inhibitor, in patients with advanced solid tumors

Abstract Background: RB1 is a tumor suppressor gene in the CDK-RB-E2F pathway and is a cell-cycle regulator to prevent uncontrolled cell proliferation. Rb binds to and inhibits E2F transcription factors to silence E2F-target genes required for S-, G2- and M-phases of the cell-cycle. Genomic alterations upstream of E2F, including RB1, can drive constitutive activation of E2F and lead to dysregulated cell proliferation. Alterations in RB1 occur in 7% of all cancers including retinoblastoma, small cell lung cancer (SCLC), neuroendocrine carcinomas, osteosarcoma, soft tissue sarcomas (STS) including leiomyosarcoma, and triple-negative breast cancer (TNBC). Patients harboring tumors with RB1 alterations have poorer treatment outcomes. CID-078 is a novel Cyclin A/B-RxL inhibitor that blocks the interaction of Cyclin A-CDK2 and CyclinB-CDK1 with their substrates, E2F and Myt1, and induces cell-cycle arrest and apoptosis in cancer cells. Methods: Patients ≥ 18 years with relapsed/refractory solid tumors are eligible to enroll in this multicenter, open label Phase 1 study (NCT06577987). CID-078 is administered orally, BID in repeating 21-day treatment cycles until disease progression or discontinuation. Dose escalation is based on the Backfill-BOIN trial design. Key objectives for the phase 1a portion of the trial are to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary anti-tumor activity of CID-078. Results: As of 16 Nov 2025, 61 patients have been enrolled across 7 dose (40 mg BID-600 mg BID). Tumor types enrolled include bone and STS (12), HR+ breast (11), TNBC (4), SCLC (5), non-small cell lung (3), squamous cell carcinoma (7) and neuroendocrine tumors (3). 46 (75%) patients harbored alterations within the cell cycle pathway including 28 (46%) RB1 alterations and 11 (18%) CDKN2A deletions, and one patient (1. 6%) harboring both RB1 alteration and a CDKN2A deletion. CID-078 has been well tolerated to date. The most common adverse events observed were nausea (28%), vomiting (18%), fatigue (18%) and diarrhea (16%) all Gr 1-2. Dose limiting G3 alanine aminotransferase increase/G4 gamma-glutamyl transferase increase was reported in 1 patient (300mg BID dose, backfill cohort). Maximum-tolerated-dose for CID-078 has not been reached. Observed human exposure was consistent with preclinical predictions of oral bioavailability of ∼20%. AUC increased in an approximately dose-proportional manner across the dose range. Biomarkers of PD in patients above 300 mg BID show on-target activity for the mechanism of action. Conclusions: Preliminary data indicate that CID-078 is orally bioavailable, safe and well tolerated in a pre-treated population with PK parameters and exposure consistent with preclinical predictions. Dose escalation is ongoing with only one DLT observed to date. Recommended dose for expansion is anticipated mid 2026. Citation Format: Afshin Dowlati, Timothy A Yap, Antonio Giordano, Nehal J. Lakhani, William B McKean, Ildefonso Ismael Rodriguez Rivera, Vivek Subbiah, Kyaw Zin Thein, Judy S. Wang, Jinshu Fang, Li-Fen Liu, Peadar Cremin, Lukas Makris, Li-Pen Tsao, Lisa M. Kopp, Shivaani Kummar. Early clinical activity from the phase 1 evaluation of CID-078, a novel Cyclin A/B-RxL inhibitor, in patients with advanced solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT023.