Clinical Trials Actively Recruiting

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.

Primary Objectives:

• To determine the maximum tolerated dose (MTD) and the dose-limiting toxicities
  (DLTs) for combination of ATR inhibitor (M1774) and BET inhibitor (ZEN003694) in
  women with recurrent clear cell, endometrioid, and platinum resistant high grade serous
  ovarian carcinoma (HGSOC) and clear cell and endometrioid endometrial carcinoma
  irrespective of ARID1A status (PART I).
• To determine safety and tolerability in ARID1A pathogenic alteration (ARID1AMUT) and
  ARID1A wildtype (ARID1AWT) cohorts (ARID1A is an integral biomarker) in an
  expansion phase (PART II).
• To determine change in pharmacodynamic biomarker expression of ƔH2AX (for ATR
  inhibition, integral biomarker) from pre-treatment and on-treatment tumor samples in
  ARID1AMUT and ARID1AWT expansion cohorts by immunohistochemistry (IHC) (PART
  II).

Secondary Objectives:

• To evaluate change in pharmacodynamic biomarker expression of cmyc (for BET inhibition,
  integrated biomarker) from pre-treatment and on-treatment tumor samples in ARID1AMUT
  and ARID1AWT expansion cohorts by Digital Spatial Profiling (DSP) (PART II).
• To evaluate change in pharmacodynamic biomarker expression of ƔH2AX (for ATR
  inhibition, integrated biomarker) from pre-treatment and on-treatment tumor samples in
  ARID1AMUT and ARID1AWT expansion cohorts by DSP (PART II).
• To investigate if ARID1A protein by IHC and DSP correlates with ARID1A pathogenic
  alteration in pre-treatment tumor biopsy samples (PART II).
• To estimate objective response rate (ORR) and progression free survival (PFS) at 6 months in
  ARID1A pathogenic alteration and wildtype cohorts (PART II).

Primary Objectives:

• To assess the safety and tolerability of BL-M07D1 in metastatic or unresectable HER2-expressing tumors
• To determine the MTD if reached or MAD and two or more RDEs of BL-M07D1

Secondary Objectives:

• To characterize the pharmacokinetics of BL-M07D1, total anti-HER2 antibody, and payload (Ed-04)
• To investigate the antitumor activity of BL-M07D1

Primary Objective:

• To characterize the safety and tolerability of MOMA-341 as monotherapy or in combination with chemotherapy or immunotherapies

Secondary Objectives:

• To identify the RP2D(s) and/or recommended optimization doses of MOMA-341 as monotherapy and in combination with chemotherapies or immunotherapies
• To characterize the PK profile of MOMA341 when administered as monotherapy and in combination with chemotherapies or immunotherapies
• To assess the effects of food on the PK parameters of MOMA-341 (for select participants only)
• To characterize the PK profile of irinotecan and its active metabolite SN-38 when administered in combination with MOMA341
• To characterize preliminary evidence of antitumor activity associated with MOMA341 as monotherapy or in combination with chemotherapies or immunotherapies

Primary Objectives:

Part 1b:

• To determine the safety and tolerability of ZN-c3 in subjects with PROC

Part 2:

• To investigate the antitumor activity of ZN-c3 in subjects with PROC

Secondary Objectives:

Part 1b:

• To investigate the antitumor activity of ZN-c3 in subjects with PROC at different doses/schedules
• To investigate the plasma PK of ZN-c3

Part 2:

• To further investigate the antitumor activity of ZN-c3 in subjects with PROC
• To investigate the safety and tolerability of ZN-c3 in subjects with PROC
• To investigate the plasma PK of ZN-c3

Primary Objective:

• To compare progression-free-survival (PFS) in patients with platinum-resistant ovarian cancer (PROC) receiving rinatabart sesutecan (Rina-S) versus investigator’s choice of therapy (IC).

Secondary Objectives:

• To assess additional measures of efficacy of Rina-S compared to IC in patients with PROC.
• To assess the safety of Rina-S compared to IC in patients with PROC
• To assess potential changes in QTc associated with Rina-S
• To assess patient reported outcomes in patients receiving Rina-S and IC

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

Randomized Phase 2 Cohort

Primary Objectives:

• To characterize the safety of the alternative dosing schedule and the US-approved dosing schedule
• To evaluate efficacy parameters of the alternative dosing schedule and the US-approved dosing schedule

Secondary Objectives:

• To investigate the frequency of ocular disorders, peripheral neuropathy, infusion reactions, and pneumonitis with 2 schedules of administration of MIRV
• To investigate the safety profiles of 2 schedules of administration of MIRV
• To evaluate additional measures of clinical efficacy with 2 schedules of administration of MIRV
• To characterize the PK of MIRV in the alternative dosing schedule, compare PK with the US-approved dosing schedule, and reassess the existing ER models
• To assess doses based on body surface area (BSA) that are equivalent to doses based on AIBW

Hepatic Impairment Cohort

Primary Objectives:

• To determine the starting dose of MIRV in patients with moderate hepatic impairment

Secondary Objectives:

• To determine the safety profile of MIRV in patients with moderate hepatic impairment

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.

Primary Objectives:

Phase 2 Simon 2-Stage Study (Arm 1 Monotherapy)

• Assess the anti-tumor activity of
  ACR-368 monotherapy in each cohort
  (ovarian, endometrial, urothelial) of
  OncoSignature Positive subjects.

Phase 1b (Arm 2 Combination Therapy)

• Assess the safety and tolerability of
  ACR-368 in combination with LDG.
• Determine the RP2D of LDG

Phase 2 Exploratory Study (Arm 2 Combination Therapy)

• Assess the anti-tumor activity of
  ACR-368 in combination with LDG in
  each cohort (ovarian, endometrial,
  urothelial) of OncoSignature Negative
  subjects.

Secondary Objectives:

Phase 2 Simon 2-Stage Study (Arm 1 Monotherapy)

• Confirmation of the OncoSignature
  thresholds for enrichment of ACR-368
  monotherapy responders.
• Assess safety and tolerability of
  ACR-368 monotherapy.
• Assess efficacy, disease control,
  survival, and landmarks of survival.
• Assess RDI every 2 months.
• Assess the PK of ACR-368 in subjects
  with ovarian carcinoma
• Assess quality of life.

Phase 1b Study (Arm 2 Combination Therapy)

• Assess the anti-tumor activity of
  ACR-368 in combination with LDG.
• Assess efficacy, disease control,
  survival, and landmarks of survival.
• Assess RDI every 2 months.
• Assess the PK of ACR-368 in
  combination with LDG.

Phase 2 Exploratory Study (Arm 2 Combination Therapy)

• Assess safety and tolerability of
  ACR-368 in combination with the
  RP2D of LDG.
• Assess efficacy, disease control,
  survival, and landmarks of survival
• Assess RDI every 2 months.