Colorectal

Key Eligibility Criteria:
Inclusion:
1. Dose Escalation additional criteria: Patients must have histologically confirmed cancer that is metastatic or unresectable and must have progressed on standard therapies which would have included fluorouracil (5-FU) or capecitabine
2. Dose Escalation additional criteria specifically for colorectal cancer (CRC) patients: Willingness and ability to undergo a pre-treatment biopsy
3. Dose Expansion additional criteria: Patients must have histologically confirmed CRC that is metastatic or unresectable and must have progressed on standard therapies which would have included 5-FU or capecitabine
4. Dose Expansion additional criteria: Willingness and ability to undergo pre- and on- treatment biopsies

Exclusion:
1. Previous treatment with BET inhibitors
2. History of inability to tolerate capecitabine at the projected treatment dose on this trial
3. Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed
4. Hepatic tumor burden > 30% or peritoneal carcinomatosis

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. Males or females aged >/= 12 to less than 85 years for Ewing sarcoma and 18 to less than 85 years of age for other tumors.
2. Part 3 combination therapy expansion tumor types:
- Histologically confirmed Ewing sarcoma with a classical fusion: Patients with locally advanced or metastatic, unresectable, relapsed, or refractory disease who have received at least 1 but no more than 2 prior lines of systemic treatment with a preferred first line chemotherapy regimens.
- Colorectal adenocarcinoma: Patients with locally advanced or metastatic, unresectable disease, who have received at least 2 but no more than 3 prior lines of systemic therapy.
3. Availability of archival tissue or fresh cancer biopsy are mandatory.

Exclusion Criteria:
1. Prior treatment with or exposure to DR5 agonists.
2. Receipt of any anticancer therapy (including investigational agents) within 4 weeks or within 5 half-lives prior to the first dose of study treatment. Exceptions per protocol.
3. Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
4. Receipt of radiotherapy within 4 weeks prior to the first dose of study treatment, and liver-directed within 12 months prior to the first dose of study drug.

For pre-screening, please contact: Message Basket: VICC RESEARCH REFERRALS/ELIGIBILITY

Key Eligibility Criteria:

Inclusion Criteria:
1. Histologically documented locally advanced and unresectable or metastatic NSCLC, PDAC, CRC, or other solid tumor with KRAS G12A, G12C, G12D, G12S, or G12V mutation
2. Measurable disease by RECIST v1.1
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1

Exclusion Criteria:
1. Malignancy within the last 2 years as specified in the protocol
2. Untreated brain metastases
3. Known hypersensitivity to BBO-11818 or its excipients

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

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. 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.