Melanoma

Eligibility Criteria
Inclusion Criteria:
1. Single agent BCA101 - patients with the following tumor type will be eligible:
a. No prior history of treatment with anti-EGFR antibodies in the unresectable/metastatic setting (prior treatment with radiotherapy in the adjuvant setting is allowed).
2. Combination BCA101 and pembrolizumab - patients with the following tumor types will be eligible:
a. Patients must have no prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease) or prior history of immune checkpoint inhibitors with the exception of neoadjuvant therapy (>6 months prior to study drug initiation). No prior history of anti-EGFR antibodies (with the exception of radiosensitizing agents and multimodal treatment for locally advanced disease).
b. Patients must provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable.
c. Patients must have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer
d. Patients must have progressed on one prior systemic therapy in the metastatic setting.
e. No prior history of treatment with anti-EGFR antibodies in the metastatic setting.
f. Expansion Cohort 6: Head and Neck Squamous Cell Carcinoma (HNSCC), metastatic or unresectable, recurrent with a Combined Positive Score (CPS) less than 1, as determined by PD-L1 IHC 22C3 pharmDx.
3. Randomized to either ficerafusp alfa alone or in combination with pembrolizumab -Expansion Cohort 9: Colorectal cancer (CRC) i. Patients must have received at least 2 and no more than 3 prior lines of systemic therapy including two standard treatment regimens.

Exclusion Criteria:
1. Prior treatment with any anti-TGFb therapy.
2. Has a history of (non-infectious) pneumonitis, radiation pneumonitis or interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.

For pre-screening, please contact: Message Basket: VICC RESEARCH PHASE 1

Key Eligibility Criteria:
Inclusion Criteria:
1. Fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis.
2. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and at least 1 lesion accessible for biopsy. Fine needle biopsy, cytology, and bone lesion biopsies are not acceptable.
3. Radiographically documented progressive disease on or after the most recent therapy.
4. Received standard-of-care therapies, (except for Part 1C, 2C and 2D, where participants with prior docetaxel use for the advanced/metastatic setting will be excluded), including an available programmed death (ligand)-1 inhibitor known to be effective in the tumor type for which they are being evaluated.
5. Advanced or metastatic disease and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant.
6. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or recurrent disease.

Exclusion Criteria:
1. Primary central nervous system (CNS) malignancy.
2. Untreated CNS metastases.
3. Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment.
4. Active, known, or suspected autoimmune disease.
5. Condition requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment.
6. History of or with active interstitial lung disease or pulmonary fibrosis.

For internal pre-screening, please contact: Epic message basket- VICC RESEARCH PHASE 1

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.

Key Eligibility Criteria:
Inclusion Criteria:
1. Subjects who have a histologically or cytologically documented metastatic or locally advanced solid tumor, for which standard of care (SoC) therapy does not exist, no longer provides benefit, or is not tolerated by the subject, or the subject has been assessed by the Investigator as not being suitable for SoC therapy.
Part B: Subjects must be diagnosed with one of the following solid tumors harboring specified genetic alterations based on a validated local test:
i. Melanoma Cohort(s):
1. Activating NRAS mutations& without known concomitant activating PIK3CA, AKT mutation or PTEN LOF
2. BRAF Class 2/3 mutations or fusions
ii. Non-Melanoma Cohorts:
1. Solid tumors with NRAS activating mutations& without known concomitant activating PIK3CA, AKT mutation or PTEN LOF
2. Solid tumors with KRAS activating mutations without known concomitant activating PIK3CA, AKT mutation of PTEN LOF
3. Solid tumors with BRAF Class 2/3 mutations or fusions
4. Glioma with BRAF Class 1, 2, or 3 mutations or fusions
2. Newly obtained or archived tumor tissue is required

Exclusion Criteria:
1. Current or history within 6 months of planned Cycle 1 Day 1 of pneumonitis or interstitial lung disease (ILD)
2. Part B: prior treatment with any MEK or BRAF inhibitor
3. A history or current evidence of significant retinal pathology leading to increased risk of retinal vein occlusion

For pre-screening, please contact: Message Basket: VICC RESEARCH PHASE 1

Key Eligibility Criteria:
Inclusion Criteria:
1. Have histologically or cytologically confirmed cancer diagnosis based on pathology report.
2. Willing to submit a pre-treatment (archival or fresh-tissue if no archival tissue is available) and on-treatment tissue sample. Additionally, during the dose-escalation portion and if appropriate in the expansion phase of the study, the Sponsor may modify subject enrolment into various cohorts that have not begun enrolling yet such that ENPP1 and/or cGAS baseline expression level in the subject's tumor must be available and may guide enrolment eligibility for the study.

Exclusion Criteria:
1. Subjects with evidence of rapid progression on prior therapy resulting in rapid clinical deterioration should be excluded from participation in the trial.
2. Uncontrolled tumor-related pain
3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
4. History or any evidence of interstitial lung disease

For internal pre-screening, please contact: Message Basket: VICC RESEARCH PHASE 1