Clinical Trials Actively Recruiting

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 Objective:

• To compare the efficacy of single-agent olaparib and the combination of olaparib and cediranib (and potentially other combination arms that may be added by subsequent amendment) versus single agent cediranib as measured by progression free survival (PFS), in patients with recurrent, persistent or metastatic endometrial cancer.

Secondary Objectives:

• To compare the efficacy of single-agent olaparib and the combination of olaparib and cediranib (and potentially other combination arms that may be added by subsequent amendment) versus single-agent cediranib as measured by overall survival (OS) in patients with recurrent, persistent or metastatic endometrial cancer.
• To compare the efficacy of single-agent olaparib and the combination of olaparib and cediranib (and potentially other combination arms may be added by subsequent amendment versus single-agent cediranib as measured by response rate in patients with recurrent, persistent or metastatic endometrial cancer.
• To assess the safety and tolerability of single–agent cediranib, single-agent olaparib, and the combination of olaparib and cediranib (and potentially other combination arms may be added by subsequent amendment).
• To assess if mutations in DNA Homologous Repair Genes (assayed prior to all treatment and prior to the study treatment) are predictive of response to olaparib alone or in combination with cediranib. (Integrated Biomarker)
• To assess if markers of angiogenesis in serial plasma samples are associated with response to cediranib alone or in combination with olaparib. (Integrated Biomarker)

Objective:

Objectives (UPLIFT):

Primary in Pivotal Cohort (UPLIFT):

• Determine the confirmed investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) in patients with higher sodium-dependent phosphate transport protein 2b (NaPi2b) expressing platinum-resistant high-grade serous ovarian cancer (HGSOC), including cancers of ovarian, fallopian tube or primary peritoneal origin)

Secondary in UPLIFT:

• Assess the investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression.
• Assess the objective response rate by independent radiology review (IRR) for patients with higher NaPi2b and overall.
• Assess the duration of objective response (DOR) in patients who achieve a response.
• Assess the incidence and severity of adverse events (AEs).

Exploratory in DES, EXP and UPLIFT:

• Retrospectively evaluate the association of objective response with tumor expression of genes other than NaPi2b, or other tumor molecular and histologic features

Exploratory in UPLIFT:

• Assess the disease control rate (DCR)
• Assess the progression-free survival (PFS)
• Assess the overall survival (OS)
• Assess the population PK
• Assess the relationship of XMT-1536 (upifitamab rilsodotin) exposure to efficacy and safety outcomes.
• Assess development of anti-drug antibody and neutralizing antibody in response to XMT-1536 (upifitamab rilsodotin) exposure

Objective:

Primary Objectives:

• To compare pembrolizumab to chemotherapy with respect to PFS per RECIST 1.1 as assessed by BICR
• Hypothesis (H1): Pembrolizumab is superior to chemotherapy with respect to PFS per RECIST 1.1 by BICR
• To compare pembrolizumab to chemotherapy with respect to OS
• Hypothesis (H2): Pembrolizumab is superior to chemotherapy with respect to OS

Secondary Objectives:

• To compare pembrolizumab to chemotherapy with respect to ORR per RECIST 1.1 by BICR in participants with measurable disease at study entry
• Hypothesis (H3): Pembrolizumab is superior to chemotherapy with respect to ORR per RECIST 1.1 by BICR in participants with measurable disease at study entry
• To compare pembrolizumab to chemotherapy with respect to DCR per RECIST 1.1 by BICR in participants with measurable disease at study entry
• To compare pembrolizumab to chemotherapy with respect to DOR per RECIST 1.1 by BICR in participants with measurable disease at study entry
• To compare pembrolizumab to chemotherapy with respect to PFS as per RECIST 1.1 assessed by the investigator
• To compare pembrolizumab to chemotherapy with respect to PFS2 as assessed by the investigator
• To compare the safety and tolerability of pembrolizumab to chemotherapy
• To compare pembrolizumab to chemotherapy with respect to change from baseline score and TTD in the EORTC QLQ-C30 GHS/QoL

Objective:

Primary Objective:

• Demonstrate superiority in Progression-free Survival (PFS) as assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 of upifitamab rilsodotin versus placebo as maintenance therapy

Key Secondary Objective:

• Compare Overall Survival (OS) of upifitamab rilsodotin versus placebo as maintenance therapy

Other Secondary Objectives:

• Compare PFS as assessed by Investigator using RECIST v1.1 of upifitamab rilsodotin versus placebo as maintenance therapy
• Compare the Objective Response Rate (ORR) as assessed by Investigator using RECIST v1.1 of upifitamab rilsodotin versus placebo as maintenance therapy
• Evaluate safety and tolerability in participants treated with upifitamab rilsodotin versus placebo as maintenance therapy

Objective:

Primary Objective:

• To determine the objective response rate (ORR) of carboplatin plus MIRV, as assessed by the investigator, in efficacy evaluable patients with recurrent platinum-sensitive, highgrade epithelial ovarian, primary peritoneal, or fallopian tube cancer (PSOC) and with folate receptor-alpha (FRα) expression of ≥ 50% of tumor cells with staining at ≥ 2+ intensity (PS2+) following 1 prior line of platinum-based chemotherapy.
  • The ORR of carboplatin plus MIRV will also be assessed, as a sensitivity analysis, by a blinded independent central review (BICR) in the same patient population.

Key Secondary Objectives:

• To determine the ORR of carboplatin plus MIRV, as assessed by the investigator, in efficacy evaluable patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity and with recurrent PSOC following 1 prior line of platinum-based chemotherapy.
  • The ORR of carboplatin plus MIRV will also be assessed, as a sensitivity analysis, by a BICR committee in the same patient population.

Additional Secondary Objectives:

• To determine the duration of response (DOR) of carboplatin plus MIRV followed by MIRV continuation as assessed by the investigator in efficacy evaluable patients with recurrent PSOC and with FRα expression of ≥ 50% of tumor cells with PS2+ staining intensity following 1 prior line of platinum-based chemotherapy. DOR analysis will be restricted to patients who achieve a response to carboplatin plus MIRV.
• To determine the DOR of carboplatin plus MIRV followed by MIRV continuation as assessed by the investigator in efficacy evaluable patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity and with recurrent PSOC following 1 prior line of latinum-based chemotherapy. DOR analysis will be restricted to patients who achieve a response to carboplatin plus MIRV.
  • DOR of carboplatin plus MIRV followed by MIRV continuation will also be assessed as a sensitivity analysis by a BICR in the 2 patient populations described above.
• To assess the following parameters in patients with recurrent PSOC following 1 prior line of platinum-based chemotherapy, treated by carboplatin plus MIRV followed by MIRV continuation:
  • Safety and tolerability of MIRV in combination with carboplatin
  • Progression-free survival (PFS) as measured by the investigator and by a BICR in patients with FRα expression of ≥ 50% of tumor cells with PS2+ staining intensity
  • PFS as measured by the investigator and by a BICR in patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity
  • Overall survival (OS) in patients with FRα expression of ≥ 50% of tumor cells with PS2+ staining intensity
  • OS in patients with FRα of ≥ 25% of tumor cells with PS2+ staining intensity
  • CA-125 response (objective restricted to patients whose CA-125 is > 2 × upper limit of normal [ULN] at baseline and thus are evaluable for Gynecologic Cancer Intergroup [GCIG] CA-125 response) as measured by the investigator in the efficacy evaluable patients with FRα expression of ≥ 50% of tumor cells with PS2+ staining intensity
  • CA-125 response as measured by the investigator in the efficacy evaluable patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity

Objective:

Primary Objectives:

• Dose Escalation (Part A): Investigate the safety and tolerability of DS-9606a and determine the maximumtolerated dose (MTD) and the recommended doses for expansion (RDE/RDEs)
• Dose Expansion (Part B): Further evaluate the safety and tolerability of DS-9606a, and investigate the overall response rate (ORR) of DS-9606a, according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) per the Investigator at the RDE/RDEs.

Secondary Objectives:

• Characterize the pharmacokinetic (PK) properties of DS-9606a, total anti-CLDN6 antibody, and the unconjugated pyrrolobenzodiazepine (PBD) payload
• Investigate the duration of response (DoR) and progression free survival (PFS) of DS-9606a, according to RECIST v1.1 per the Investigator
• Assess the immunogenicity of DS-9606a

Objective:

Primary Objectives:

• Determine the maximum tolerated dose (MTD) of CB-03-10 in subjects with advanced solid tumors
• Determine the dose-limiting toxicity (DLT) of CB-03-10 in subjects with advanced solid tumors

Secondary Objectives:

• Determine a recommended Phase 2 dose (RP2D) of CB-03-10
• Determine the safety profile of CB-03-10 in subjects with advanced solid tumors
• Evaluate the activity (response rate, PFS, and OS) of CB-03-10 in subjects with specific solid tumors (e.g., relapsed/refractory pancreatic adenocarcinoma, androgen independent prostate adenocarcinoma, relapsed/refractory triple-negative breast adenocarcinoma)
• Characterize the pharmacokinetics (PK) of CB-03-10 and its metabolite CB-03-05 as well as cortexolone in plasma and urine.

Objective:

Primary Objectives:

• To determine clinical benefit as described by the overall response rate (ORR) of nab-sirolimus via independent radiographic review (IRR) in patients with malignant solid tumors with pathogenic inactivating alterations in TSC1 or TSC2 genes

Secondary Objectives:

• To evaluate the duration of response (DOR), disease control rate (DCR), time to response (TTR), and progression-free survival (PFS) via IRR, and overall survival (OS) of nab-sirolimus
• To evaluate changes in Quality-of-Life
• To describe the safety and tolerability of nab-sirolimus