Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Immune System Diseases

Breast Neoplasms

Neoplasm Metastasis

Hypersensitivity

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Niraparib

Olaparib

Mitogens

Adenosine

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients with advanced or metastatic cancer will receive ART6043 administered in 21-day cycles.

Patients with advanced or metastatic cancer and with PARPi as an appropriate treatment option will receive ART6043 in combination with Olaparib twice daily (BID) in 21-day cycles.

Patients with advanced or metastatic cancer and with PARPi as an appropriate treatment option will be given ART6043 in combination with Niraparib once daily (QD) in 21-day cycles.

Patients with g/sBRCA-m, HER2-ve locally advanced or metastatic breast cancer will be randomly assigned to receive ART6043 in combination with a PARPi or a PARPi alone (Olaparib and Niraparib).

ART6043

Patients will orally receive ART6043 in combination with Olaparib.

Patients will orally receive ART6043 combination with Niraparib.

Artios Pharma

This interventional study will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART6043 as monotherapy or in combination with Olaparib or Niraparib.

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: Part A (dose-escalation phase) \& Part B (dose-expansion phase).

Part A will evaluate ART6043 as monotherapy (Part A1) in patients with advanced or metastatic cancer and in combination with either Olaparib (Part A2) or Niraparib (Part A3), in patients with advanced or metastatic cancer with genetic lesions that cause loss of function of known DNA Damage Response (DDR) genes. Olaparib or Niraparib are collectively referred to as PARPi.

Part B will evaluate the preliminary efficacy, safety profile, and PK of ART6043 in combination with a PARPi compared to PARPi alone. Part B will randomize patients with human epidermal growth factor receptor 2 negative (HER2-ve) locally advanced or metastatic breast cancer with a germline or somatic breast cancer gene (BRCA) mutation (g/sBRCA-m) who have received no or ≤1 month of prior treatment with a PARPi, in a 1:1 to an RP2D of ART6043 in combination with a PARPi vs a PARPi alone.

Patients may continue to receive ART6043 and/or PARPi 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 of ART6043 in Advanced/Metastatic Solid Tumors Patients

A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the DNA Polymerase Theta Inhibitor ART6043 Administered Orally as Monotherapy and in Combination to Patients With Advanced or Metastatic Solid Tumors

Severity of adverse events as assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

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.

To assess the safety and tolerability of ART6043 given orally in combination with PARPi at the Recommended Phase II dose(s) \[RP2D(s)\].

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.

Objective Response Rate (ORR) is defined as the proportion of patients with a CR or PR to treatment according to RECIST v1.1.

To assess preliminary signs of efficacy for ART6043 as monotherapy, in combination with Olaparib and in combination with Niraparib.

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.

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.

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.

OS is defined as the time from the start of study treatment (Part A) or randomization (Part B) until death due to any cause.

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 and in combination with Niraparib. Also, to explore the effect of ART6043 on the Cmax of Olaparib and Niraparib.

To determine the t1/2 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 and in combination with Niraparib. Also, to explore the effect of ART6043 on the t1/2 of Olaparib and Niraparib.

To determine the AUC0-inf 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 and in combination with Niraparib. Also, to explore the effect of ART6043 on the AUC0-inf of Olaparib and Niraparib.

To determine renal clearance 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 and in combination with Niraparib.

To determine percent of ART6043 excreted in urine following single oral dosing of ART6043.

To assess CA-125 levels in pre-dose tumor samples that may be predictive of the activity of ART6043.

Spots Global Cancer Trial Database for sensitivity to polymerase theta inhibitor