Breast

Key Eligibility Criteria:

Inclusion:
1. For Phase 1b: locally advanced, recurrent, or metastatic, incurable, and histologically or cytologically confirmed HR+/HER2- breast cancer by ASCO/CAP criteria (based on most recent assessment):
a) Must have received CDK4/6i in the adjuvant or metastatic setting, unless patient was unable or unwilling to receive standard of care CDK4/6i treatment; or must be able to receive it on protocol, AND,
b) Received no more than 1 prior line of therapy containing chemotherapy (including cytotoxic antibody-drug conjugates) given in the metastatic setting; AND,
c) Must have received no more than 3 lines of therapy in total for metastatic disease.
d) May have received a prior PI3Ka inhibitor

NOTE: If the patient progressed on the PI3K inhibitor a sample (tissue or liquid) must have been obtained following progression, or at study screening, to be analyzed at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory, determine the resistance mutation(s) and Sponsor approval for study inclusion obtained. If the patient was intolerant to the drug, then mutational analysis and Sponsor approval are not required for enrollment.

Exclusion:
1. Has had tumor evaluated for PTEN and AKT and has known mutations or deletions in PTEN, or, activating mutations in AKT (E17K) determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory (e.g., ISO15189-certified, in-house clinical testing).
2. Metaplastic breast cancer
3. Possible allergies to TOS-358 or excipients


For pre-screening, please contact: Message Basket: P VICC RESEARCH BREAST OHO

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:
1. Patient has a histologically- or cytologically confirmed cancer that is advanced, recurrent, or metastatic with the following origins, and whose disease progressed on standard therapy and for whom there are no alternative therapies that may confer overall survival benefit:
a. For Patients in the Dose Escalation Part:
i. Platinum-resistant ovarian cancer (PROC)
1. Histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer, with predominantly high-grade (Grade 2 or 3) epithelial features (serous and clear cell)
2. Platinum resistant is defined as relapsed within 6 months after the last dose of platinum-based therapy
ii. Triple negative breast cancer (TNBC)
1. ER- and PR-negative with HER2 negative
2. HER2 negative is defined as one of the following: 0 or 1+ by IHC, or if IHC 2+, then in situ hybridization is negative per the ASCO-CAP HER2 guidelines
3. ER- and PR-negative is defined as < 10% of cells expressing hormonal receptors by IHC, as per standard guidelines
iii. Squamous cell carcinoma of the anus (SCCA)
1. Patient with locally advanced ineligible for surgery is allowed.
iv. Squamous cell carcinoma of the head and neck (SCCHN)
v. Non-small cell lung cancer (NSCLC: adenocarcinoma, large cell, and squamous cell carcinoma)
vi. Uterine serous cancer (recurrent or persistent)
b. For Patients in the Dose Expansion Part:
i. Cohort A: PROC (same as above)
ii. Cohort B: TNBC (same as above)
iii. Cohort C: SCCA (same as above)
2. For Dose Expansion only: Patient has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and, if only one target lesion is present, has not received prior radiotherapy to the target lesion

Exclusion:
1. Patient has received prior treatment at any time with a cell cycle checkpoint inhibitor (eg, CHK1 and/or CHK2, WEE1, or ATR inhibition)


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.