Endometrial

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 Criteria:
1. Disease-specific Inclusion Criteria in Phase 1b Expansion Cohorts: Ovarian Cancer
a) Histologically or cytologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma. Carcinosarcomas are also eligible.
b) Participants who had received one line of platinum-based therapy must have received at least four cycles of their initial platinum-containing regimen, had a response (complete or partial), and then had disease progression between 3 and 6 months after their last dose. Participants who had previously received two or three lines of platinum-based therapy must have had disease progression while receiving the therapy or within 6 months after the last dose.
c) At least 1 but no more than 4 prior lines of systemic therapy.

2. Disease-specific Inclusion Criteria in Phase 1b Expansion Cohorts: Endometrial Cancer
a) Histologically confirmed endometrial adenocarcinoma regardless of mismatch repair deficiency status.
b)Relapsed or progressive disease after at least one prior line of systemic therapy.
c)Disease not amenable to curative surgery or radiation.
d)At least 1 but no more than 3 prior lines of systemic therapy in any setting. Prior endocrine therapy is not counted as a prior line of systemic therapy.

Disease-specific Inclusion Criteria in Phase 1b Expansion Cohorts: Cholangiocarcinoma
a) Histologically or cytologically confirmed advanced cholangiocarcinoma (intrahepatic, extrahepatic, or hilar). Advanced gallbladder adenocarcinomas are also eligible. Ampullary carcinomas are not eligible in Phase 1b.
b) Unresectable, locally advanced, or metastatic disease.
c) Disease progression during or after at least one prior line of systemic therapy for advanced disease.
d) At least 1 but no more than 3 prior lines of systemic therapy for advanced disease.

Exclusion Criteria:
1. Participant has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
2. Participant has received previous treatment with another agent targeting CD24.
3. Disease-specific Exclusion Criteria in Phase 1b Expansion Cohorts: Ovarian Cancer
a) Non-epithelial ovarian tumors or ovarian tumors of low malignant potential
4. Disease-specific Exclusion Criteria in Phase 1b Expansion Cohorts: Endometrial Cancer
a) Carcinosarcoma histology
5. Disease-specific Exclusion Criteria in Phase 1b Expansion Cohorts: Cholangiocarcinoma
a) Ampullary carcinoma (unless specifically cholangiocarcinoma histology)
b) Gallbladder cancers other than adenocarcinomas.

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.

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