Study of ART6043 in Advanced/Metastatic Solid Tumors Patients

Phase 2Active Not RecruitingNCT05898399

Artios Pharma Ltd220 enrolled

Overview

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 in combination with olaparib (Part B1) and to assess initial effectiveness of ART6043 in combination compared to olaparib alone (Part B2) in patients with certain types of 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

220

Conditions

Advanced Solid Tumor Metastatic Solid Tumor

Interventions

ART6043DRUG

ART6043 will be given orally.

OlaparibDRUG

Olaparib will be given orally.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients who have discontinued all previous chemotherapeutic agents, non-hormonal targeted therapy, or investigational drugs for at least 21 days or 5 half-lives (not including palliative radiotherapy at focal sites), whichever is shorter. Endocrine and hormonal therapies for the treatment of cancer must have been discontinued (unless for the treatment of Prostate Cancer) at least 7 days before receiving study medication. Palliative radiotherapy must have completed prior to start of study treatment. * Resolution of all toxicities of prior therapy or surgical procedures. * Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale. * Have adequate organ function. * Patients of childbearing potential and patients with partners of childbearing potential are required to use highly effective contraception. * Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator. Inclusion Criteria specific to Part A1 (ART6043 as Monotherapy) • Advanced or metastatic cancer. Tumors with genetic lesions known to cause loss of function of known DDR genes based on available pre-existing testing are encouraged. Inclusion criteria specific to Part A2 (ART6043 in combination with olaparib) * Advanced or metastatic cancer with genetic lesions known to cause loss of function of known DDR genes based on available, pre-existing testing. * Patients for whom a PARPi is an appropriate treatment option. Patients may have received prior treatment with a PARPi. Inclusion criteria specific to Part B (ART6043 in combination with olaparib or olaparib alone) * Histologically or cytologically confirmed HER2-ve locally advanced or metastatic carcinoma of the breast. * Documentation of a deleterious or suspected deleterious g/sBRCA mutation. * No more than 3 prior chemotherapy-inclusive schedules (including antibody conjugates) for locally advanced and/or metastatic disease. * Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, or metastatic setting unless medically contraindicated. * Patients must have received no or ≤1 month of prior treatment with a PARPi. Exclusion Criteria: * Patients who are pregnant. * Patients with Myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML) or with features suggestive of MDS/AML. * Have ongoing interstitial lung disease or pneumonitis. * Have any major gastrointestinal issues that could impact absorption of ART6043 or olaparib. * Patients with brain metastases (patients with treated brain metastases could be eligible if follow-up brain imaging after central nervous system-directed therapy shows no evidence of progression). * Have received a live vaccine within 30 days before the first dose of study treatment. * Recent major surgery within 4 weeks prior to entry into the study. * Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment. * Have a history of allergy or hypersensitivity to study drug components. Exclusion criteria specific to Part B * First-line locally advanced and/or metastatic breast cancer with no prior adjuvant chemotherapy. * Inflammatory breast cancer.

Locations (7)

South Texas Accelerated Research Therapeutics (START) - Midwest

Grand Rapids, Michigan, United States

Memorial Sloan-Kettering Cancer Center (MSKCC)

New York, New York, United States

Stephenson Cancer Center - Oncology

Oklahoma City, Oklahoma, United States

Jefferson University Hospitals - Kimmel Cancer Center

Outcomes

Primary Outcomes

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 B1: 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)

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).

Secondary Outcomes

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)

Data from ClinicalTrials.gov

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