Clinical Trials Actively Recruiting

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:

• 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:

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 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 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:

Phase 1

• To identify potential OBRD and dosing regimens of MBRC-101
• To establish the MTD of MBRC-101 using 1 or more dosing regimens
• To identify potential RP2Ds and regimens of MBRC-101

Phase 1b

• To evaluate the safety of MBRC-101 at potential OBRDs, RP2Ds and dosing regimens
• To evaluate preliminary clinical activity of MBRC-101 at potential OBRDs and dosing regimens

Phase 2

• To evaluate the efficacy of MBRC-101 at the RP2D

Secondary Objectives:

Phase 1

• To evaluate other measures of preliminary clinical activity of MBRC-101

Phase 2

• To evaluate other measures of clinical activity
• To evaluate the safety of MBRC-101 at RP2Ds and dosing regimens

Phase 1/1b and Phase 2

• To characterize single and multiple-dose PK profiles of MBRC-101
• To evaluate incidence and persistence of anti-MBRC-101 Ab formation
• To evaluate biomarkers of clinical response and resistance, safety, pharmacodynamic activity, and/or mechanism of action of MBRC-101

Primary Objectives:

• To characterize the safety and tolerability of TYRA-430 in participants with advanced hepatocellular carcinoma and other solid tumors with FGF/FGFR pathway alterations

Secondary Objectives:

• To characterize the PK profile of TYRA-430 and its metabolite and to correlate drug exposure with safety assessments and measures of antitumor activity
• To evaluate the preliminary antitumor activity of the optimal dose of TYRA-430 in participants with advanced, previously treated hepatocellular carcinoma

Primary Objective:

Dose Escalation

• To characterize the safety, tolerability, DLT and MTD (or maximum administered dose [MAD] or maximum biologically effective dose [MBED] if no MTD defined) of CLN-619 administered intravenously alone (Module A, Module D) or in combination with pembrolizumab (Module B) or in combination with chemotherapy (Module C) in patients with advanced solid tumors.

Dose Expansion

• To evaluate the anti-tumor activity of CLN-619 alone and/or in combination with pembrolizumab (Module B) or with chemotherapy (Module C), as assessed by the Best Overall Response (BOR), ORR, Duration of Response (DoR), Progression Free Survival (PFS), Disease Control Rate (DCR), Overall Survival (OS), and the Clinical Benefit Rate (CBR), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, in patients with advanced solid tumors.

Secondary Objectives:

• To assess the PK profile of CLN-619 administered alone, - in combination with pembrolizumab or in combination with chemotherapy in patients with selected, advanced solid tumors.
• To assess the immunogenicity of CLN-619 administered alone, in combination with pembrolizumab, or in combination with chemotherapy, in patients with selected, advanced solid tumors.

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