This interventional study will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART6043 as monotherapy or in combination with olaparib.
ART6043 is being developed as an oral anti-cancer agent in combination with a poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor (PARPi) in patients with cancers that harbor defects in DNA repair. The study will consist of two parts: 1. Part A (Dose-escalation phase): Part A will evaluate ART6043 as monotherapy (Part A1) in patients with advanced or metastatic cancer and in combination with olaparib (Part A2), in patients with advanced or metastatic cancer with genetic lesions that cause loss of function of known DNA Damage Response (DDR) genes. Olaparib is also referred as PARPi. 2. Part B (dose-expansion phase): To further confirm the safety of ART6043 and assess its initial effectiveness in combination compared to olaparib alone (Part B2) in patients with a germline BRCA mutation who have HER2-ve advanced or metastatic breast cancer Patients may continue to receive ART6043 and/or olaparib as long as they may be continuing to derive clinical benefit as assessed by the investigator and/or until disease progression, withdrawal of consent or until they experience unacceptable drug-related toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
181
South Texas Accelerated Research Therapeutics (START) - Midwest
Grand Rapids, Michigan, United States
ACTIVE_NOT_RECRUITINGMemorial Sloan-Kettering Cancer Center (MSKCC)
New York, New York, United States
Part A: Number of participants with Dose Limiting Toxicities (DLTs)
Severity of adverse events as assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: From first dose of study treatment until the end of Cycle 1 (each cycle is 21-days)
Part B2: Progression free survival (PFS)
PFS is defined as the time from randomization until objective disease progression as defined by Response evaluation criteria in solid tumors (RECIST) v1.1 or death by any cause in the absence of progression, regardless of whether the patient withdraws from study medication or receives another anti-cancer therapy prior to progression.
Time frame: Until disease progression (Upto 3.7 years).
Part B2: Number of participants with Adverse events
To assess the safety and tolerability of ART6043 given orally in combination with olaparib at the Recommended Phase II dose(s) \[RP2D(s)\].
Time frame: Screening (≤28 days) Until follow-up visit (90 days after discontinuation)] (up to 3.7 years)
Best overall response (BOR)
The best overall response is the best response (complete response \[CR\] or partial response \[PR\]) recorded from the date of randomization for each patient until the progression or censoring date in the absence of progression.
Time frame: Screening (≤28 days) Until disease progression/recurrence (Upto 3.7 years)
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the proportion of patients with a CR or PR to treatment according to RECIST v1.1.
Time frame: Screening (≤28 days) Until disease progression/recurrence (Upto 3.7 years)
Disease control rate (DCR)
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Stephenson Cancer Center - Oncology
Oklahoma City, Oklahoma, United States
ACTIVE_NOT_RECRUITINGJefferson University Hospitals - Kimmel Cancer Center
Philadelphia, Pennsylvania, United States
ACTIVE_NOT_RECRUITINGSCRI oncology partners
Nashville, Tennessee, United States
COMPLETEDMary Crowley Cancer Center - Clinic
Dallas, Texas, United States
COMPLETEDThe University of Texas - MD Anderson Cancer Center
Houston, Texas, United States
ACTIVE_NOT_RECRUITINGHospital Universitario Clínico San Cecilio
Granada, Andalusia, Spain
RECRUITINGHospital Clínico Universitario de Valladolid
Valladolid, Castille and León, Spain
RECRUITINGHospital de la Santa Creu i Sant Pau
Barcelona, Catalonia, Spain
RECRUITING...and 2 more locations
To assess preliminary signs of efficacy for ART6043 as monotherapy and in combination with olaparib.
Time frame: Screening (≤28 days) Until disease progression (Upto 3.7 years)
Duration of response (DOR)
The DOR will be defined for patients with a BOR of CR/PR (with a Prostate Cancer Working Group \[3PCWG-3\] response of non-PD/NE for patients with prostate cancer), as the time from the date of first documented response until date of documented progression (by RECIST v1.1 or PCWG-3) or death in the absence of disease progression.
Time frame: Screening (≤28 days) Until disease progression (Upto 3.7 years)
Change in tumor size
The best percentage change in tumor size from baseline will be determined for each patient, ie, the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction.
Time frame: Screening (≤28 days) Until disease progression (Upto 3.7 years)
Change in level of cancer antigen 125 (CA-125)
To assess preliminary signs of efficacy for ART6043 as monotherapy and in combination with olaparib.
Time frame: Screening (≤28 days) Until follow-up visit (Upto 3.7 years)
Part A: Progression free survival (PFS)
The PFS is defined as the time from randomization until the earliest objective disease progression defined by RECIST v1.1 or PCWG-3 (for patients with prostate cancer in Arm 2) or death by any cause in the absence of progression, regardless of whether the patient withdraws from study medication or receives another anti-cancer therapy prior to progression.
Time frame: Screening (≤28 days) Until disease progression (Upto 3.7 years)
Overall survival (OS)
OS is defined as the time from the start of study treatment (Part A) or randomization (Part B) until death due to any cause.
Time frame: Screening (≤28 days) Until overall survival follow-up (Upto 3.7 years)
Plasma concentration
To determine the plasma concentration of ART6043 and its potential active metabolite ART7276 following both single and multiple oral dosing of ART6043 monotherapy and following multiple oral dosing of ART6043 in combination with olaparib.
Time frame: Pre-dose Cycle 0 Days -2, -1 , Cycle 1 Days 1, 8, 15, 16, Cycle 2 Days 1, 8, 15, Cycle 3 Day 1 Upto 3.7 Years (Each Cycle is 21-Days)
Cancer antigen 125 levels in pre-dose tumor samples
To assess CA-125 levels in pre-dose tumor samples that may be predictive of the activity of ART6043.
Time frame: At Screening (≤28 days)