Cervical

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. Histologic diagnosis of locally advanced or metastatic solid tumor malignancy (except CNS primary malignancy, for example, glioma), and where applicable, with an FGFR3 pathway alteration listed in Section 10.8, on molecular testing in tumor or blood sample that is deemed as actionable, as defined below per specified cohort.
2. Cohort B: Locally Advanced or Metastatic Urothelial Carcinoma
a. B1: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib and EV
b. B2: LOXO-435 monotherapy- mUC, Qualifying FGFR3 alterations, ≥1 prior regimen, FGFR inhibitor naïve
c. B4: LOXO-435 monotherapy- mUC, ≥2 prior regimens, including erdafitinib; EV naïve
d. B5: LOXO-435 + Pembrolizumab + EV- mUC, Qualifying FGFR3 alterations, No prior systemic therapy
3. Cohort C: Locally Advanced or Metastatic Solid Tumors (Non-Urothelial Carcinoma)
a. C1: LOXO-435 monotherapy- Qualifying FGFR3 alterations, Progressed/intolerant to available standard therapies, FGFR inhibitor naïve
4. Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review

Exclusion Criteria:
1. Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
2. For Cohort B5 only, individuals with known uncontrolled diabetes.
3. For Cohorts B3 and B5 only, individuals with a history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
4. Individuals with uncontrolled hypercalcemia <14 days to C1D1.


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

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.