Clinical Trials Actively Recruiting

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 determine if overall survival (OS) is improved with proton beam therapy (PBT) treatment as compared to intensity modulated radiation therapy (IMRT) as part of planned protocol treatment for patients with esophageal cancer.
• To determine if OS with PBT is non-inferior to IMRT as part of planned protocol treatment and that there will be less grade 3+ cardiopulmonary toxicity with PBT than with IMRT.

Secondary Objectives:

• To compare the symptom burden and impact on functioning of patients between treatment modalities based on Patient Reported Outcome (PRO) measures of symptoms using MD Anderson Symptom Inventory (MDASI) and PROMIS-Fatigue;
• To compare the Quality-Adjusted Life Years (QALY) using EQ5D as a health outcome (Kilbridge 2010) between PBT and IMRT, if the protocol primary endpoint is met;
• To assess the pathologic response rate between PBT and IMRT;
• To assess the cost-benefit economic analysis of treatment between radiation modalities;
• To compare the length of hospitalization after protocol surgery between PBT and IMRT;
• To compare the incidence of grade 4 lymphopenia during chemoradiation between PBT and IMRT;
• To compare lymphocyte nadir at first follow-up visit after completion of chemoradiation between PBT & IMRT;
• To estimate the locoregional failure, distant metastatic free survival, and progression-free survival of patients treated with PBT versus IMRT;
• To compare incidence of both early (< 90 days from treatment start) and late (≥ 90 days from treatment start) cardiovascular and pulmonary events between PBT versus IMRT;
• To compare the Total Toxicity Burden (TTB) of IMRT versus PBT based on a composite index of 9 individual cardiopulmonary toxicities.

Exploratory Objectives:

• To collect biospecimens for future analyses, for example to assess cardiac and inflammatory biomarkers in association with treatment complications.

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 Objective:

Dose-escalation and Dose-expansion Cohorts

• To determine the safety profile, maximum tolerable dose (MTD), minimally reproducible active dose (MRAD), and recommended dose range (RDR) of BHV-1530 administered by IV infusion dosed Q3W.

Dose-confirmation Cohorts

• To determine the recommended dose (RD) of BHV-1530 for later phase trials.

Secondary Objectives:

Dose-escalation and Dose-expansion Cohorts

• To assess the preliminary efficacy of BHV-1530
• To determine the PK of BHV-1530, total antibody, and free payload TopoIx (BHC-0080269)
• To assess the incidence of antidrug antibody (ADA) against BHV-1530

Dose-confirmation Cohort

• To assess the preliminary efficacy of BHV-1530
• To determine the PK of BHV-1530, total antibody, and free payload TopoIx BHC-0080269
• To assess the incidence of ADA against BHV-1530

Dose-Escalation Part (Part 1)

Primary Objectives:

• To assess the safety and tolerability of YL217 in patients with advanced solid tumors
• To determine the maximum tolerated dose (MTD) of YL217 in patients with advanced solid tumors

Secondary Objectives:

• To characterize the pharmacokinetics (PK) of YL217 antibody-drug conjugate (YL217-ADC), YL217 total antibody (YL217-TAb), and unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
• To evaluate immunogenicity as measured by the presence of anti-drug antibodies (ADAs) in patients treated with YL217
• To document any preliminary efficacy of YL217 in patients with advanced solid tumors

Backfill Part (Part 2)

Primary Objectives:

• To further evaluate the safety and tolerability of YL217 in patients with advanced solid tumors
• To determine the recommended dose(s) for expansion (RDE(s)) of YL217 in patients with advanced solid tumors

Secondary Objectives:

• To further evaluate the efficacy of YL217 in patients with advanced solid tumors
• To characterize the PK of YL217-ADC, YL217-TAb, unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
• To evaluate immunogenicity as measured by the presence of ADAs in patients treated with YL217

Dose-Expansion Part (Part 3)

Primary Objectives:

• To further evaluate the efficacy of YL217 at the RDE(s) in patients with the selected advanced solid tumors such as colorectal adenocarcinoma, gastric, esophageal or gastroesophageal junction adenocarcinoma, and pancreatic adenocarcinoma
• To determine the recommended phase 2 dose (RP2D) of YL217

Secondary Objectives:

• To further evaluate the safety and tolerability of YL217 at the RDE(s) in patients with the selected advanced solid tumors
• To characterize the PK of YL217-ADC, YL217-TAb, unconjugated payload YL0010014, metabolite YL0010034 and, if applicable, other potential metabolite(s)
• To evaluate immunogenicity as measured by the presence of ADAs in patients treated with YL217

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 evaluate overall survival after the combination of fruquintinib and AM RF EMF treatment in patients with refractory metastatic colorectal cancer

Secondary Objectives:

• To evaluate the safety and tolerability of the combination of fruquintinib and AM RF EMF treatment in patients with refractory metastatic colorectal cancer
• To evaluate the progression-free survival rate after the combination of fruquintinib and AM RF EMF treatment in patients with refractory metastatic colorectal cancer
• To evaluate the rates of disease progression every 6 months up to 60 months after the combination of fruquintinib and AM RF EMF treatment in patients with refractory metastatic colorectal cancer

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 Objective:

• To determine if overall survival (OS) is improved in patients who received mFOLFIRINOX +/- nivolumab in comparison to FOLFOX +/- nivolumab as first-line chemotherapy for metastatic gastroesophageal adenocarcinoma.

Secondary Objectives:

• To compare other indices of efficacy, including progression-free survival, objective response rates and duration of response between both treatment arms
• To evaluate safety and tolerability associated with treatment in each of the treatment arms
• To evaluate the proportion of patients receiving second line of therapy in both arms
• To evaluate tolerability of the treatment in both arms using PRO-CTCAE

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