Hepatocellular

Key Eligibility Criteria:

Inclusion Criteria:
1. Dose Expansion only:
a. Patients who have at least one measurable lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline >/=10 mm in the longest diameter.
b. Mandatory provision of tumor tissue sample from a recent biopsy in a quantity sufficient to allow for analysis
c. All patients with biliary tract cancer or other solid tumor malignancies should have HER2 testing performed using a local laboratory
d. Cohort 1
i. Confirmed HER2-positive (IHC3+, or IHC2+ and ISH*+), locally advanced/unresectable or metastatic biliary tract cancer, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary adenocarcinoma (*ISH: FISH, SISH, or DISH)
ii. Failed or intolerant to at least 1 prior gemcitabine- and/or cisplatin-based therapy with/without immune checkpoint inhibitors as per available local standards
e. Cohort 2
i. Pathologically confirmed HER2-positive (IHC3+, or IHC2+ and ISH*+), locally advanced/unresectable or metastatic solid tumor malignancy other than breast and gastric or gastroesophageal junction adenocarcinoma and biliary tract cancer (*ISH: FISH, SISH, or DISH)
ii. Patients who have received all available standard therapies known to provide clinical benefit, and have no currently available treatment options due to disease progression, intolerance or other reasons

Exclusion Criteria:
1. History of (non-infectious) interstitial lung disease (ILD) or pneumonitis that required steroids, or any evidence of current ILD or pneumonitis.
2. Systemic steroid therapy (>10 mg daily prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
3. Previous treatment with a 4-1BB/CD137-modulating agent.

For pre-screening, please contact: Your disease specific research team.

Key Eligibility Criteria:
Inclusion Criteria:

1. Patient must have undergone RNA testing in a Clinical Laboratory Improvement Act (CLIA) environment or must submit archival tissue to determine RNA overexpression of ADC TOIs by the TARGET Assay. Patients who have high TOI RNA expression will have confirmation of TOI expression by CLIA IHC assay at MD Anderson Cancer Center (MDACC).

2. COHORT A: Patient must have high Trop-2 protein expression (IHC 2+ or 3+) excluding advanced colorectal cancer, urothelial cancer, head and neck cancer (Note: exceptions include patients with adenoid cystic cancer, salivary gland cancer, thyroid cancer, and parathyroid cancer, who are eligible), triple negative breast cancer (TNBC), HR-positive breast cancer, HER2-positive breast cancer, small cell lung cancer, NSCLC, and endometrial cancer

3. COHORT B: Patient must have high Nectin-4 protein expression (IHC 2+ or 3+) excluding advanced urothelial cancer, head and neck cancer (to include salivary gland cancer and adenoid cystic cancer), breast cancer, lung cancer, gastric cancer, gastroesophageal junction cancer, esophageal cancer, prostate cancer, or penile cancer

4. COHORT C: Patient must have HER2 protein expression (IHC 2+ or 3+) excluding advanced breast cancer, non-small cell lung cancer (NSCLC), colorectal carcinoma (CRC), gastric cancer, or gastroesophageal junction (GEJ) cancer

Exclusion Criteria:

1. Active or chronic corneal disorder including, but not limited to, Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and/or active ocular conditions requiring ongoing treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the ADCs used in the study
3. History of interstitial lung disease or pneumonitis requiring steroid therapy


For pre-screening, please contact: Individual research disease teams.