Clinical Trials Actively Recruiting

Primary Objectives

Among patients with metastatic extrapulmonary poorly differentiated small cell NEC, to compare overall survival (OS, measured from randomization) in a fixed sequence as follows:

• Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus induction platinum/etoposide alone (Arm 3)
• Compare the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2) versus induction platinum/etoposide alone (Arm 3)
• Compare the combination of induction platinum/etoposide and atezolizumab followed by maintenance atezolizumab (Arm 1) versus the combination of induction platinum/etoposide and atezolizumab followed by observation (Arm 2)

Secondary Objective(s)

• To compare OS, measured from start of observation/maintenance, across arms
• To compare progression-free survival (PFS) (measured from randomization and measured from start of observation/maintenance) across arms
• To compare objective response rate (ORR = confirmed and unconfirmed partial response (PR) + confirmed and unconfirmed complete response (CR)) across arms among patients with measurable disease at randomization
• To compare clinical benefit rate (CBR = confirmed and unconfirmed PR + confirmed and unconfirmed CR + stable disease (SD)) across arms among patients with measurable disease at randomization
• To compare the duration of response (DOR) across arms
• To evaluate the safety and tolerability of each arm

Additional Objective

• To bank tumor and blood samples for future biomarker correlative studies
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Part 1 and Part 2

Primary Objectives:

• To evaluate the safety and tolerability of IMP1734 as monotherapy and in combination with anti-cancer agents
• To determine the MTD (or MAD) and RDE as monotherapy and in combination with anti-cancer
  agents

Secondary Objectives:

• To characterize the plasma PK profile of single and multiple doses of IMP1734
• To assess preliminary anti-tumor activity of IMP1734 as monotherapy and in combination with anti-cancer agents

Part 3

Primary Objectives:

• To estimate the anti-tumor activity of IMP1734

Secondary Objectives:

• To further assess the anti-tumor activity of IMP1734
• To further evaluate the safety and tolerability of IMP1734

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

Primary Objectives:

• To determine the safety and tolerability of OBI-992 when administered intravenously (IV) to subjects with advanced solid tumors
• To determine the maximum tolerated dose (MTD) and optimal recommended Phase 2 dose (RP2D) of OBI-992 using randomized assignment to 2 dose level cohorts and assessment of activity, safety, and tolerability for each cohort
• To evaluate the preliminary clinical activity profile of OBI-992 (objective response rate [ORR], clinical benefit rate [CBR], duration of response [DOR], disease control rate [DCR], and progression-free survival [PFS])

Secondary Objectives:

• To determine the serum pharmacokinetics (PK) of OBI-992 and its active metabolite exatecan
• To evaluate the immunogenicity of OBI992 (anti-drug antibodies [ADAs])

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 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

Primary Objectives:

• Determine efficacy using proportion of patients alive and progression-free at 4 months within each cancer subtype

Secondary Objectives:

• Determine overall response rate (ORR), duration of response (DoR), median progression-free survival (PFS) and overall survival (OS) within each cancer subtype
• Determine safety and tolerability in each cancer subtype

Primary Objective:

• To determine whether de-intensified chemoradiation for early stage SCCA is able to maintain excellent 2year disease control of 85% or higher while improving anorectal HRQL, compared to standard-dose CRT, as measured by the change in the FIQoL instrument coping/behavior domain from baseline to 1 year.

Secondary Objectives:

• To compare changes in patient-reported outcomes (as per FISI, PROMIS, IIEF, SVQ, and VAS/VuAS instruments) between the experimental and control arm.
• To compare patterns of failure (local and regional relapse versus distant; infield versus out-of-field of radiation), disease control, and overall survival between experimental and control arm.
• To correlate vaginal dilator use during radiation delivery with sexual function.
• To measure changes in serum total testosterone from baseline to up to 12 months after radiation.
• To validate the utility of image features of inguinal and pelvic lymph nodes obtained prior to treatment as a prognostic indicator that can identify patients with early-stage anal squamous cell carcinoma for whom treatment with de-intensified chemo-radiation is appropriate.
• To determine whether an online, interactive educational tool (eContour) may improve the quality of radiation target delineation for anal cancer.
• To determine the incidence of and predictors for cardiovascular toxicity in patients receiving 5-FU or Capecitabine.

Primary Objective:

• To assess the efficacy of TARE followed by durvalumab monotherapy followed by durvalumab +bevacizumab by assessment of PFS in participants with unresectable HCC amenable to locoregional therapy

Secondary Objectives:

• To assess the safety of the sequence of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy
• To assess ORR after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy
• To assess OS after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy
• To assess DoR after TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy

Primary Objectives:

All Phases

• To characterize the safety and tolerability of FMC-376 in participants with locally advanced unresectable or metastatic solid tumors with KRAS G12C mutation
• To characterize the PKs profile of FMC-376
• To evaluate the anti-tumor activity of FMC-376 using RECIST v1.1

Phase 1 (A & B) Only

• To establish the MTD and/or the RP2D and regimen of FMC-376