Phase 1 Study of RBN-2397, an Oral PARP7 Inhibitor, in Patients With Solid Tumors

Dose Escalation Phase only: Metastatic or advanced-stage solid malignant tumor (which may include "solid" lymphoma [e.g., mantle cell]) for whom no therapy exists that would be curative or might provide clinical benefit.

Dose Expansion Phase Only: Patients with locally advanced or metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have received standard therapy or are intolerant of standard therapy, have progressed following their last prior therapy, and have one of the following tumor types:

• SCCL: Histologically confirmed NSCLC of predominantly squamous cell histology and must have received no more than 3 lines of prior systemic therapy including chemotherapy regimens and/or immune checkpoint inhibitor therapy (combination allowed).
• HNSCC: Histologically confirmed squamous cell carcinoma of the head and neck (either HPV-positive or -negative) and must have received no more than 3 lines of prior systemic immunotherapy and/or chemotherapeutic treatments in the metastatic setting. Includes primary tumor location of the oral cavity, oropharynx, hypopharynx, larynx, and paranasal sinuses (nasopharyngeal carcinoma, skin squamous cell carcinoma, and salivary gland carcinomas are not eligible).
• HR+ breast cancer: Histologically confirmed diagnosis of estrogen receptor (ER) and/or progesterone receptor (PR) positive, HER2-negative adenocarcinoma of breast (as per local laboratory testing) whose disease has failed standard systemic therapy for locally advanced or metastatic disease and must have received no more than 1 prior chemotherapeutic for advanced/metastatic disease.
• PARP7 amplified: Tumor with documented PARP7 (or TIPARP) gene copy amplification as determined by a CLIA certified laboratory test (e.g., FoundationOne CDx) that has failed standard systemic therapy for locally advanced or metastatic disease.

Must agree to undergo tumor biopsy Normal organ and bone marrow function Patient and his/her partner agree to use adequate contraception during and for 3 months after the last study drug dose

Exclusion Criteria:

• Unable to swallow oral medications
• Major surgery within 4 weeks of starting study
• Pregnant or breast-feeding.
• Receiving intravenous antibiotics for an active infection
• Known human immunodeficiency virus (HIV) or hepatitis B or C infection.
• History of a different malignancy unless disease-free for at least 5 years
• Some medications are not allowed while on study. Interested participants will need to inform study doctor of all the medications he/she is taking.
• Herbal medicines, and grapefruit, grapefruit juice, pomegranate juice, star fruit or orange marmalade (made with Seville oranges) are not allowed to be taken during study.