Primary Outcome Measures:
- Number of Participants with Dose Limiting Toxicities (DLTs) [Time Frame: Days 1-21 (Cycle 1)]
- Number of Participants with Adverse Events (AEs), AE of Special Interest (AESIs), and Serious AEs (SAEs) [Time Frame: Up to 34 months]
- Dose Escalation (Arm 1a): Participant has histologically confirmed locally advanced or metastatic cancer (cutaneous melanoma, non-small-cell lung carcinoma (NSCLC), non-muscle invasive bladder cancer, head and neck squamous cell carcinoma, Microsatellite stable colorectal cancer (MSS CRC), basal cell carcinoma, or triple negative breast cancer) with measurable disease as determined by RECIST v1.1. Arm 1a participants must have received, and then progressed, relapsed, or been intolerant to, or ineligible for, at least 1 standard treatment regimen in the advanced or metastatic setting. Participants with a known driver mutation must have also received or been offered a mutation-directed therapy, where indicated. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.
- Dose Confirmation (Arm 1b): Participant has histologically confirmed locally advanced or metastatic, and checkpoint inhibitor refractory melanoma or locally advanced or metastatic, and checkpoint inhibitor refractory NSCLC with measurable disease as determined by RECIST v1.1 who have disease progression after, at least 1 line of standard therapy (no limit to prior lines of therapy), and have been treated with or refused standard of care treatment. Must have primary refractory or acquired secondary resistance to prior immune checkpoint treatments. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.
- NSCLC participants with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), proto-oncogen tyrosine-protein kinase reactive oxygen species (ROS1), or other actionable mutations for which there are approved targeted therapies, must have received prior approved targeted therapy or have been offered and declined approved targeted therapy.
- Dose Expansion Arm (Arm 2) only: Participant has histologically confirmed locally advanced, metastatic melanoma, or locally advanced or metastatic NSCLC with a PD-L1 TPS of ≥1%, with measurable disease as determined by RECIST v1.1 and have not had any prior therapy for this cancer in this setting. Participants must have a tumor lesion amenable to biopsy and must provide tumor biopsy sample at baseline. If the participant is undergoing a new biopsy, they must have another lesion that can be followed for response.
- Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
- Participant has adequate hematological and biological function.
- Participant has active central nervous system tumors or metastases.
- Participant has received treatment with prohibited medications (that is, concurrent anticancer therapy including other chemotherapy, radiation [local radiation for palliative care is permitted with approval from the Sponsor], hormonal anticancer treatment, biologic therapy, or immunotherapy) or investigational agents within 5 half-lives or 14 days prior to the first day of study intervention, whichever is shorter.
- Participant has required the use of additional immunosuppression other than corticosteroids for the management of an AE, has experienced recurrence of an AE if rechallenged, and currently requires maintenance doses of >10 milligrams (mg) prednisone or equivalent per day.
- Participant has any plan to receive a live attenuated vaccine during study intervention or has received a live vaccine within 30 days before the first dose of study intervention.
- Participant has reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline.
- Female participant who is pregnant, breastfeeding, or is of childbearing potential (WCBP), defined as all women capable of becoming pregnant unless they are using 2 highly effective methods of contraception during dosing and for 90 days after the last dose administrations.
- Sexually active males who refuse to use a condom during intercourse while taking study intervention and for 90 days after stopping study intervention and should not father a child in this period.
- Participant has any unstable or clinically significant concurrent medical condition that would, in the opinion of the Investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol.
- Participant has concurrent enrollment in another clinical study (unless it is an observational noninterventional clinical study) or during the follow-up period of an interventional study.
- Other inclusion/exclusion criteria are present. Please contact the study team for a complete list.
Julie Bauman, MD
Contact Phone Number