Clinical Trials Actively Recruiting

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 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).

Objective:

Primary Objectives:

• To evaluate the anti-tumor activity of genetically modified autologous T-cells (ADP-A2M4CD8) as monotherapy and in combination with nivolumab in HLA-A*02 positive subjects with MAGE-A4 positive recurrent ovarian cancer

Secondary Objectives:

• To evaluate the safety and tolerability of genetically modified autologous T-cells (ADP-A2M4CD8) as monotherapy and in combination with nivolumab in HLA-A*02 positive subjects with MAGE-A4 positive recurrent ovarian cancer
• To further evaluate the anti-tumor activity of genetically modified autologous T-cells (ADP-A2M4CD8) as monotherapy and in combination with nivolumab in HLA-A*02 positive subjects with MAGE-A4 positive recurrent ovarian cancer
• To characterize the surrogates of treatment effect

Objective:

Primary Objective:

• To compare the progression-free survival (PFS) of the combination of avutometinib plus defactinib vs Investigator’s Choice of Treatment (ICT) in patients with recurrent LGSOC

Secondary Objectives:

• To compare the combination of avutometinib plus defactinib vs ICT in patients with recurrent LGSOC with regard to additional efficacy parameters
• To characterize the safety and tolerability of combination avutometinib plus defactinib vs ICT in patients with recurrent LGSOC
• To determine the exposure of avutometinib and defactinib in patients with recurrent LGSOC treated with combination of avutometinib plus defactinib
• To assess the health-related quality of life and disease related symptoms in patients with recurrent LGSOC treated with combination avutometinib plus defactinib vs ICT

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:

• 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.

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 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.

Objective:

Primary Objectives:

• To assess the safety and tolerability of study drug
• To identify the recommended dose(s) (RD[s]) and schedule(s) that is (are) safe and biologically effective for study drug administered by intravenous (IV) dosing
• To identify the RD(s) and schedule(s) that is (are) safe and biologically effective for study drug administered by subcutaneous (SC) dosing

Secondary Objectives:

• To characterize the pharmacokinetics (PK) of study drug administered by IV dosing
• To characterize the PK of study drug administered by SC dosing
• To assess the preliminary antitumor activity of study drug

Objective:

Dose-Escalation Phase

Co-Primary Objectives:

• To assess safety and tolerability, including dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), or maximum administered dose (MAD; if no MTD is defined) of IMGN151 when administered intravenously
• To determine recommended Phase 2 dose (RP2D) for IMGN151

Secondary Objectives:

• To characterize the pharmacokinetics (PK) and immunogenicity of IMGN151
• To assess objective response rate (ORR) for IMGN151 using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• To assess duration of response (DOR) for IMGN151 using RECIST v1.1

Expansion Phase

Primary Objective:

• To assess ORR for IMGN151 using RECIST v1.1

Secondary Objectives:

• To characterize safety and tolerability for IMGN151
• To characterize the PK and immunogenicity of IMGN151
• To assess DOR for IMGN151
• To assess PFS for IMGN151