Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Immune System Diseases

Neoplasm Metastasis

Breast Neoplasms

Hypersensitivity

Neoplastic Processes

Antineoplastic Agents

All Drugs and Chemicals

Niraparib

Mitogens

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Part A1 will evaluate ART4215 monotherapy administered in 21 day cycles. Up to 90 participants will participate in this dose escalation arm.

Part A2 will evaluate ART4215 given in combination with talazoparib in 21 day cycles. Up to 50 participants will participate in this dose escalation arm.

In Part B1 dose expansion, up to 30 participants with solid cancers that have been treated with a PARP inhibitor for an approved indication will receive ART4215.

In Part B2 dose expansion, up to 20 participants with solid cancers with characteristics indicative of sensitivity to pol theta inhibition will receive ART4215.

In Part B3, approximately 120 participants with HER2 negative BRCA breast cancers will be randomized 1:1 to either ART4215 in combination with talazoparib or talazoparib alone.

Part A3 will evaluate ART4215 given in combination with niraparib in 21-day cycles. Up to 30 participants will participate in this dose escalation arm.

Participants will receive ART4215 by mouth daily in 21-day cycles.

ART4215

Talazoparib will be administered at a dose of 1 mg or 0.75 mg by mouth daily in 21-day cycles.

Niraparib will be administered at a dose of 200 mg or 300 mg by mouth daily in 21-day cycles.

Erika Hamilton, MD

Timothy Yap, MBBS, PhD

This clinical trial is evaluating a drug called ART4215 in participants with advanced or metastatic solid tumors. The main goals of this study are to:

* Find the recommended dose of ART4215 that can be given safely to participants alone and in combination with talazoparib
* Learn more about the side effects of ART4215 alone and in combination with talazoparib
* Learn more about the effectiveness of ART4215 alone and in combination with talazoparib
* Learn more about the effectiveness of ART4215 alone and in combination with niraparib

This is an open-label Phase I/IIa study designed to evaluate ART4215, a new first-in-class investigational medicinal product that is a potent and selective inhibitor of deoxyribonucleic acid (DNA) polymerase (pol) theta. ART4215 is being developed as an oral anti-cancer agent for monotherapy treatment of patients with cancers that harbor defects in DNA repair and in combination with anticancer medicines that cause DNA damage.

A Study of ART4215 for the Treatment of Advanced or Metastatic Solid Tumors

A Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the DNA Polymerase Theta Inhibitor ART4215 Administered Orally as Monotherapy and in Combination to Patients With Advanced or Metastatic Solid Tumors

DLTs are defined as adverse events (graded according to NCI CTCAE v5.0) during Cycle 1 that are related to ART4215 monotherapy, in combination with talazoparib or in combination with niraparib

Number of adverse events as characterized by type, frequency, seriousness (graded according to NCI CTCAE v5.0) and relationship to ART4215

PFS is defined as the time from the start of randomization until the earliest objective disease progression defined by RECIST v1.1 or death by any cause in the absence of progression.

Number of adverse events as characterized by type, frequency, seriousness (graded according to NCI CTCAE v5.0) and relationship to ART4215 in combination with talazoparib

BOR will be calculated as the best response from date study treatment started until progression or censoring date in the absence of progression. BOR will be based on RECIST v1.1 and Prostate Cancer Working Group-3 (PCWG-3) (for prostate cancer).

ORR is defined as the proportion of patients who have a best response of either complete response (CR) or partial response (PR) based on RECIST v1.1 or PCWG-3. Response must be confirmed (at least two responses of CR or PR a minimum of 4 weeks apart and prior to progression/subsequent therapy) for Parts A, B1 and B2.

DCR is defined as the proportion of patients with CR, PR, or SD based on RECIST v1.1 or PCWG-3.

DOR will be defined for patients with a BOR of CR/PR 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. BOR should be confirmed in Parts A, B1, and B2.

Change in tumor size will be assessed for all patients with target lesion measurements at baseline.

PFS is defined as the time from the start of study treatment until the earliest objective disease progression defined by RECIST v1.1 or PCWG-3 or death by any cause in the absence of progression.

OS is defined as the time from the start of study treatment until death due to any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of ART4215 for the Treatment of Advanced or Metastatic Solid Tumors	NCT04991480	Advanced Cancer Metastatic Canc... Breast Cancer	ART4215 Talazoparib Niraparib	18 Years -	Artios Pharma Ltd
A Study of ART4215 for the Treatment of Advanced or Metastatic Solid Tumors	NCT04991480	Advanced Cancer Metastatic Canc... Breast Cancer	ART4215 Talazoparib Niraparib	18 Years -	Artios Pharma Ltd

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