Objective:

Primary Objectives:

• Phase II: Progression Free Survival
  To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma. Efficacy will be determined via investigator assessed progression free survival (PFS) as assessed by RECIST 1.1. The two experimental arms (Arms 2 and 3) will be compared to the reference arm (Arm 1). If the experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.
• Phase III: Overall Survival
  To evaluate the efficacy of trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) and pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO) in combination with paclitaxel/carboplatin in patients with HER2 positive endometrial serous carcinoma or carcinosarcoma. Efficacy will be determined via investigator assessed overall survival (OS). The two experimental arms (Arms 2 and 3) will be compared to the reference arm (Arm 1). If the experimental arms demonstrate superiority to the reference, the experimental arms will be compared to each other.

Secondary Objectives:

• To evaluate the overall response rate (ORR) in patients with measurable disease. The ORR will be defined as the binomial proportion of evaluable patients with a best overall response of CR or PR (by RECIST 1.1) within 12 months of initiating maintenance therapy.
• To evaluate the duration of objective response in patients with measurable disease as assessed by RECIST 1.1.
• To determine the nature, frequency and degree of toxicity as assessed by CTCAE v.5.0 for each treatment arm.
• To compare QOL, as measured by FACT-En-TOI, in the experimental versus control arms.
• To compare patient-reported treatment-associated symptoms (diarrhea and rash) as measured with the PRO -CTCAE, patient-reported fatigue as measured with the PROMIS-Fatigue short form, and worry concerning side effects of treatment as measured by the item ‘bothered by side effect’, in the FACT-En TOI, respectively, in the experimental and control arms.
• To assess the correlation of HER2 IHC expression and ISH amplification with clinical outcome and response to HER2 targeted therapies.

Objective:
Primary Objective:

• To examine if letrozole monotherapy/maintenance is non-inferior to IV paclitaxel/carboplatin and maintenance letrozole with respect to PFS in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.

Secondary Objectives:

• To compare the nature, frequency and maximum degree of toxicity as assessed by CTCAE v5.0 for each treatment arm.
• To compare the relative frequency of objective tumor response in those with measurable disease after cytoreductive surgery for each treatment arm.
• To compare overall survival for each treatment arm.
• To compare the CT\L and L\L arms with respect to patients adherence to letrozole therapy as measured by pill counts.

Objective:

Primary Objective:

• To compare the non-inferiority of bilateral salpingectomy (BLS) with delayed oophorectomy to bilateral salpingo-oophorectomy (BSO) to reduce the risk of ovarian cancer among women with deleterious BRCA1 germ-line mutations.

Secondary Objectives:

• To prospectively assess estrogen deprivation symptoms in BLS patients as measured by the FACTES sub-scale compared to women in the BSO arm.
• To determine if health-related QOL (FACT) is negatively impacted by menopausal symptoms (menopausal symptom checklist-MSCL), sexual dysfunction (FSFI), and cancer distress (IES) in women who have undergone BLS, in comparison to normative data (MSCL/FACT-ES) and data from BSO patients.
• To assess medical decision making, as measured by the Shared Decision Making Questionnaire (SDM-Q-9) and Decision Regret Scale (DRS), and determine factors associated with the risk of reducing surgical treatment choice.
• To assess adverse events, graded using CTCAE v5.0.

Objective:

Primary Objectives:

• To investigate the safety of monotherapy and T- Plex combination TCR-Ts
• To determine the recommended phase 2 dose of monotherapy and T- Plex combination TCR-Ts

Secondary Objectives:

• To investigate preliminary anti-tumor activity of monotherapy and T- Plex combination TCR-Ts
• To investigate the feasibility of repeat dosing of monotherapy and T- Plex combination TCR-Ts

Objective:

Dose Escalation

Primary Objective

• To assess the safety and tolerability of AB598 in patients with advanced malignancies

Secondary Objectives

• To describe the PK profile of AB598 in patients with advanced malignancies
• To assess the immunogenicity to AB598 in patients with advanced malignancies
• To assess the clinical activity of AB598 in participants with advanced malignancies

Dose Expansion

Primary Objective

• To characterize the safety and tolerability of AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies

Secondary Objectives

• To characterize the PK profile of AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies
• To assess the immunogenicity to AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies
• To assess the clinical activity of AB598 in combination with zimberelimab and standard chemotherapies in participants with advanced malignancies

Objective:

Primary Objective:

• To evaluate the antitumor activity of disitamab vedotin in subjects with previously treated, locally-advanced unresectable or metastatic (LA/m) HER2 expressing solid tumors

Secondary Objectives:

• To evaluate the safety and tolerability profile of disitamab vedotin
• To assess other measures of antitumor activity of disitamab vedotin per investigator assessment by other clinically relevant measures
• To evaluate the pharmacokinetics (PK) of disitamab vedotin
• To evaluate the immunogenicity of disitamab vedotin

Objective:

Primary Objective:

• To evaluate the antitumor activity of nemvaleukin alfa (‘nemvaleukin’, ALKS 4230)in combination with pembrolizumab as compared with chemotherapy in patients with platinum-resistant ovarian cancer

Secondary Objectives:

• To evaluate the antitumor activity of nemvaleukin in combination with pembrolizumab as compared with chemotherapy
• To evaluate the safety of nemvaleukin in combination with pembrolizumab as compared with chemotherapy

Objective:

Primary Objectives:

• To evaluate the efficacy of selinexor compared to placebo as maintenance therapy

Key Secondary Objectives:

• To compare overall OS in selinexor and placebo arms

Secondary Objectives:

• To evaluate the safety and tolerability of selinexor
• To compare selinexor and placebo for time to first subsequent therapy
• To compare selinexor and placebo for time to second subsequent therapy
• To compare selinexor and placebo for time until second progression
• To assess the efficacy of selinexor compared to placebo, as assessed by a blinded independent central review (BICR)
• To evaluate health-related quality of life (HRQoL) outcomes

Objective:

Primary Objective:

• To compare the rates of lower extremity limb dysfunction (defined as a ≥4-point increase in GCLQ symptom score from baseline) in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy:
  
  • Arm 1: Sentinel lymph node mapping followed by side-specific lymphadenectomy on sides without a SLN identified according to an NCCN Guidelines approved algorithm.
  • Arm 2: Sentinel lymph node mapping according to an NCCN Guidelines approved algorithm followed by bilateral pelvic +/- para-aortic lymphadenectomy.

Secondary Objectives:

• To compare changes in lower extremity limb circumference in patients with apparent uterine confined endometrial cancer randomized to one of two lymphatic assessment strategies at time of hysterectomy. A subset of study sites will also assess limb changes over time using lower extremity bioimpedance devices.
• To validate the test characteristics of a SLN mapping algorithm including SLN detection rates, rate of perioperative complications, rate of identifying lymphatic metastases, and detection of micrometastases using pathologic ultra-staging.

Objective:

Primary Objective:

• The primary objective is to determine Progression-free Survival (PFS) by RECIST 1.1.

Key Secondary Objectives:

• To determine Objective Response Rate (ORR) and Duration of Response (DOR) by RECIST 1.1, PFS by RECIST 1.1 (in modified population), PFS by iRECIST, Overall Survival (OS), and safety.

Key Other Objectives:

• To determine ORR by the Gynecological Cancer Intergroup (GCIG) CA-125 criteria, and Clinical Benefit Rate [CBR = (CR + PR + SD ≥ 15 weeks)/total # of patients evaluated by RECIST 1.1 or iRECIST]. Additional analyses of efficacy endpoints in modified population are included.