Gynecologic Cancer

Key Eligibility
1.Patients with newly diagnosed, pathologically confirmed, FIGO Stage III or IV ovarian cancer of the following types:
∙ high grade serous,
∙ high grade endometrioid, and/or
∙ other epithelial ovarian cancer with BRCA1/2 deleterious alteration (germline or somatic).
Submission of pathology report is required.
2. Patients must have:
a) Documented variant (tumor or germline) in BRCA1 or BRCA2 that is predicted to be pathogenic or suspected pathogenic (deleterious alteration).
∙ Submission of testing report is required.
OR
b) BRCA 1/2 wildtype AND known HRD deficient tumor determined by any commercial or academic, CLIA-certified laboratory (e.g., Myriad MyChoice©)
∙ Submission of testing report is required.
Prior Treatment
• Patient must have undergone cytoreductive surgery (primary or interval).
• Patients must have completed first line platinum-based therapy prior to registration:
• Platinum based chemotherapy course must have consisted of a minimum of 4 treatment cycles and a maximum of 9, although it is strongly recommended that patients receive at least 6 cycles unless medically contraindicated.
• For those receiving less than 6 cycles of platinum-based therapy, the reason for this must be documented and could include hematologic toxicity or non-hematologic toxicities directly related to therapy.
• Intravenous, intraperitoneal, or neoadjuvant platinum-based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle.
• Patients must not have received an investigational agent during their first line course of chemotherapy.
• Patients must have, in the opinion of the investigator, no clinical evidence of disease progression following completion of this chemotherapy course (partial or complete response to platinum-based chemotherapy).
• Patients with treated brain metastases are eligible if follow up brain imaging after CNS directed therapy shows no evidence of progression and patients are neurologically stable off steroid therapy.
• Patients must be randomized at least 3 weeks and no more than 12 weeks after their last dose of chemotherapy (last dose is the day of the last infusion of platinum agent).
• No previous treatment with a PARP inhibitor, including olaparib, niraparib, and rucaparib.
• ECOG Performance Status of ≤ 2

Key Eligibility
Newly diagnosed AJCC Stage I, II, III testicular NSGCT
1. Observation Only Arm: AJCC Stage IA, IB, IS, Age less than 50 years old
Monthly tumor marker assessment x 1 year, q2 months for year 2, then q6 months for years 3 and 4.
CXR and abdomen/pelvis CT scan are required at 3 and 12 months.
2. Standard Risk 2 Arm: AJCC Stage II, II, and IGCCC Good Risk, age less than 25 years old.
Patients are randomized between receiving 3 cycles of BEP or BEC
Cycles are 21 days with visits on Day 1-5, 8 and 15. Next cycle begins on Day 22 or when eligibility
criteria are met .

Ovarian Germ Cell Tumors
1. Low risk stratum
No age limit
Newly diagnosed stage I, grade 2 or 3 immature teratoma
2. Standard risk 2 stratum
Age > 11 and < 25
Stage II-IV GCT containing yolk sac tumor and/or embryonal carcinoma and/or choriocarcinoma
3. Visit Summary:
Low risk stratum: Observation with tumor markers q 2 mos first year, q 3 months 2nd year, annually 3rd year, then as clinically
indicated. Imaging at 4 and 12 months in first year, then as clinically indicated.
Standard risk 1 stratum: 4 cycles of chemotherapy q 3 weeks
Standard risk 2 stratum: 3 cycles of chemotherapy q 4 weeks

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

Patient Eligibility Criteria:
-- Have histologically confirmed high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Mixed tumors are permitted if they are predominantly high grade serous or endometrioid histology.
Note: Ovarian carcinosarcomas are eligible.
-- Have FRα status determined prior to randomization, by IHC test using anti-FOLR1 antibody clone FOLR1-2.1 performed in CLIA, ISO/IEC, CAP, or similarly certified laboratories as per local guidelines including, but not limited to, IVDR compliance as applicable.
-- ECOG performance status of 0-1

Inclusion Criteria Part A (PROC) only:
-- Have platinum-resistant disease, defined as radiographic progression </=6 months (that is, </=182 days) of the last administration of platinum therapy.
Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
-- Candidate for subsequent treatment with paclitaxel, PLD, gemcitabine, topotecan, or MIRV, per investigators judgement and local approved label.

Previous treatment
-- Have previously received >/= 1 but </= 3 prior lines of systemic cytotoxic therapy. Up to 4 lines of prior therapy is allowed if one of those lines is MIRV.
-- Have received prior bevacizumab treatment, unless documented contraindication or intolerance.
-- Have received treatment with a PARPi if known to have a somatic or germline BRCA mutation, if clinically indicated, unless documented contraindication or intolerance.

Inclusion Criteria Part B (PSOC) only:
-- Have relapsed after first-line platinum-based chemotherapy and have platinum-sensitive disease defined as radiographic progression >6 months (that is, >182 days) after their last administration of platinum therapy.
Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
-- Candidate for subsequent treatment with a platinum doublet (carboplatin/paclitaxel, carboplatin/gemcitabine, or carboplatin/PLD) and bevacizumab, per investigators judgement.

Previous treatment
-- Have previously received >/= 1 but </= 2 prior lines of systemic cytotoxic chemotherapy, and a PARPi, per local product label, with progression on, or within 6 months (that is, within 182 days) of completion of PARPi treatment.
Note: Prior bevacizumab is permitted.

Key Eligibility Criteria:
1. Patients must have histologically confirmed recurrent platinum-resistant EOC of any histology, as defined by progression within 6 months of the last dose of platinum-based chemotherapy. Both primary platinum resistant and acquired platinum resistant patients are allowed. Stage IV disease must have complete response of extra-abdominal disease on preoperative imaging or deemed resectable with iCRS.
2. Patients must have received 1-3 prior systemic therapies.
3. ECOG performance status </= 2

Eligibility Criteria - Dose Expansion Only
1. High-grade serous histology is required.
2. For the dose expansion cohort, patients must have measurable disease that is amenable to biopsy for correlative studies, specifically at least 1 tumor accessible and safe for biopsy on office exam or tumor that a radiologist deems is safe for biopsy in interventional radiology department based on imaging.

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

Patient Eligibility Criteria:
-- Have histologically confirmed high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Mixed tumors are permitted if they are predominantly high grade serous or endometrioid histology.
Note: Ovarian carcinosarcomas are eligible.
-- Have FRα status determined prior to randomization, by IHC test using anti-FOLR1 antibody clone FOLR1-2.1 performed in CLIA, ISO/IEC, CAP, or similarly certified laboratories as per local guidelines including, but not limited to, IVDR compliance as applicable.
-- ECOG performance status of 0-1

Inclusion Criteria Part A (PROC) only:
-- Have platinum-resistant disease, defined as radiographic progression </=6 months (that is, </=182 days) of the last administration of platinum therapy.
Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
-- Candidate for subsequent treatment with paclitaxel, PLD, gemcitabine, topotecan, or MIRV, per investigators judgement and local approved label.

Previous treatment
-- Have previously received >/= 1 but </= 3 prior lines of systemic cytotoxic therapy. Up to 4 lines of prior therapy is allowed if one of those lines is MIRV.
-- Have received prior bevacizumab treatment, unless documented contraindication or intolerance.
-- Have received treatment with a PARPi if known to have a somatic or germline BRCA mutation, if clinically indicated, unless documented contraindication or intolerance.

Inclusion Criteria Part B (PSOC) only:
-- Have relapsed after first-line platinum-based chemotherapy and have platinum-sensitive disease defined as radiographic progression >6 months (that is, >182 days) after their last administration of platinum therapy.
Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression.
-- Candidate for subsequent treatment with a platinum doublet (carboplatin/paclitaxel, carboplatin/gemcitabine, or carboplatin/PLD) and bevacizumab, per investigators judgement.

Previous treatment
-- Have previously received >/= 1 but </= 2 prior lines of systemic cytotoxic chemotherapy, and a PARPi, per local product label, with progression on, or within 6 months (that is, within 182 days) of completion of PARPi treatment.
Note: Prior bevacizumab is permitted.

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. 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

1. Documentation of Disease
-Stage III and Stage IVA endometrial cancers (with measurable disease),
-Stage IVB endometrial cancer (with or without measurable disease), or
-Recurrent endometrial cancer (with or without measurable disease) See Appendix I for FIGO 2009 Staging
2. Histologic confirmation of the original primary tumor is required (submission of pathology report(s) is required). Patients with the following histologic types are eligible: endometrioid, serous, dedifferentiated/undifferentiated, clear cell, mixed epithelial, carcinosarcoma, adenocarcinoma not otherwise specified (N.O.S.)
3. Patients must have: Tumoral mismatch repair proficient (pMMR) disease as assessed by immunohistochemistry (IHC)
AND
4. P53 IHC with aberrant staining pattern (aberrant p53 expression is consistent with mutant TP53). TP53 mutation by next-generation sequencing will also be accepted.
5. ECOG Performance Status of </= 2

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