Histologically or cytologically documented refractory solid tumors that are recurrent or metastatic including: HNSCC (excluding EBV-positive nasopharyngeal carcinoma), NSCLC, esophageal/gastric cancer, colorectal cancer, endometrial carcinoma, urothelial carcinoma, and breast cancer (HR-positive \[HER2-positive or HER2-negative\] and TNBC subtype)
Age ≥ 18 years
Life expectancy of at least 3 months
Willingness and ability to comply with the study protocol and long
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1-term follow-up (LTFU) assessments
Has received standard systemic therapies with known clinical benefit, or is considered inappropriate for such therapies, in the opinion of the investigator. In the dose escalation Phases (Parts 1A and 1C), there is no limit on the number of prior therapies
Expansion Phase (Part 1B) only: Up to two prior therapies are allowed. For participants with AGA-driven adenocarcinoma NSCLC up to four prior therapies are allowed
Measurable disease per RECIST v1.1.
Adequate hematologic and organ function
You may not be if
Prior anticancer treatment with an ADC with a TOP1 inhibitor payload. (Prior therapy with an ITGB6-targeted ADC is otherwise allowed.)
Prior anticancer therapy (prior to first dose of study treatment): chemotherapy within ≤ 2 weeks, ICI ≤ 3 weeks, ADCs ≤ 3 weeks, palliative radiation therapy ≤ 2 weeks, and major surgery ≤ 4 weeks of C1D1. If not specified, ≥ 5 half-lives or 2 weeks, whichever is longer, since administration of prior therapy must have elapsed
Residual Common Terminology Criteria for Adverse Events (CTCAE) v5 ≥ Grade 2 toxicity from prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 peripheral neuropathy, which is controlled, and endocrinopathies secondary to prior ICI controlled by hormonal treatment. For Part 1C only: discontinued prior immunotherapy due to treatment-related toxicity
Untreated or active brain metastases and/or leptomeningeal disease
Participants with active ILD or active, non-infectious pneumonitis or a history of active pneumonitis ≤ 6 months from the first dose of study treatment
Significant, concurrent renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease that could impact participation in this clinical trial
Previous solid organ or bone marrow transplantation
Concurrent participation in another therapeutic treatment trial
