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

NCT04991480 | Completed Phase 1 FDA Drug

• 1 other identifier: ART4215C001
• Study Type: interventional
• Target: 93
• Locations: 2 countries
• Sites: 8

Brief Summary

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

Conditions

Advanced Cancer; Breast Cancer; Metastatic Cancer

Keywords

Sensitivity to pol theta inhibition; Germline Breast Cancer gene mutation; gBRCA-m; BRCA1; BRCA2; Human epidermal growth factor receptor 2 negative; HER2 negative

Outcome Measures

Primary Outcomes (3)

• Part A: Number of participants with dose limiting toxicities (DLTs) from ART4215 monotherapy, in combination with talazoparib or in combination with niraparib

  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

  21 days (Cycle 1)

• Part B1 and B2: Number of participants with adverse events following administration of ART4215

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

  From the first dose until up to 30 days after the last dose of ART4215. Each cycle is 21 days.

• Part B3: Progression free survival (PFS) as a measure of efficacy for ART4215 in combination with talazoparib or talazoparib alone

  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.

  Every 6 weeks (±7 days) from date of randomization for 18 weeks, then every 9 weeks (±7 days) up to approximately 24 months. Each cycle is 21 days.

Secondary Outcomes (21)

• Part B3: Number of participants with adverse events following administration of ART4215 in combination with talazoparib

  From the first dose until up to 30 days after the last dose of ART4215. Each cycle is 21 days.

• Best overall response (BOR) as a measure of efficacy for ART4215 as monotherapy, in combination with talazoparib or in combination with niraparib

  Every 6 weeks (±7 days) from the first dose for 18 weeks, then every 9 weeks (±7 days) up to approximately 24 months. Each cycle is 21 days.

• Objective response rate (ORR) as a measure of efficacy for ART4215 as monotherapy, in combination with talazoparib or in combination with niraparib

  Every 6 weeks (±7 days) from the first dose for 18 weeks, then every 9 weeks (±7 days) up to approximately 24 months. Each cycle is 21 days.

• Disease control rate (DCR) as a measure of efficacy for ART4215 as monotherapy, in combination with talazoparib or in combination with niraparib

  Every 6 weeks (±7 days) from the first dose for 18 weeks, then every 9 weeks (±7 days) up to approximately 24 months. Each cycle is 21 days.

• Duration of response (DOR) as a measure of efficacy for ART4215 as monotherapy, in combination with talazoparib or in combination with niraparib

  Every 6 weeks (±7 days) from the first dose for 18 weeks, then every 9 weeks (±7 days) up to approximately 24 months. Each cycle is 21 days.

Study Arms (6)

Part A1

EXPERIMENTAL

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

Drug: ART4215

Part A2

EXPERIMENTAL

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.

Drug: ART4215; Drug: Talazoparib

Part B1

EXPERIMENTAL

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.

Drug: ART4215

Part B2

EXPERIMENTAL

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

Drug: ART4215

Part B3

EXPERIMENTAL

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.

Drug: ART4215; Drug: Talazoparib

Part A3

EXPERIMENTAL

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.

Drug: ART4215; Drug: Niraparib

Interventions

ART4215 DRUG

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

Part A1; Part A2; Part A3; Part B1; Part B2; Part B3

Talazoparib DRUG

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

Also known as: Talzenna

Part A2; Part B3

Niraparib DRUG

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

Also known as: Zejula

Part A3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Discontinued all previous treatments for cancer for at least 21 days or 5 half-lives, whichever is shorter (except in Germany where local regulation requires the longer of 21 days or 5 half-lives washout), and recovered from the acute effects of therapy. Palliative radiotherapy must have completed 1 week prior to start of study treatment.
• At least 1 radiologically evaluable lesion (measurable and/or non-measurable) that can be assessed at baseline and is suitable for repeated radiological evaluation by RECIST v1.1 or Prostate Cancer Working Group-3 (PCWG-3) for patients with prostate cancer
• Acceptable hematologic, renal, hepatic, and coagulation functions independent of transfusions and granulocyte colony-stimulating factor
• Willingness to abide by protocol defined contraceptive requirements for the duration of the study.
• Estimated life expectancy of ≥12 weeks
• Advanced or metastatic cancer, which is refractory to standard therapies, or for which no standard therapies exist, or for which the investigator feels no other active therapy is required for the duration of the study
• Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available for submission for analysis
• Advanced or metastatic cancer for which a PARP inhibitor is an appropriate treatment option. Participants may have received prior treatment with PARP inhibitor
• Optional baseline biopsy for BRCA1/2 mutations and prior PARP inhibitor
• Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available for submission for analysis
• Advanced or metastatic cancer for which a PARP inhibitor is an appropriate treatment option. Prior treatment with PARP inhibitor
• Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available for submission for analysis
• Advanced or metastatic solid tumors that have undergone disease progression during treatment with a PARP inhibitor for an approved indication
• At least 1 measurable lesion assessable using standard techniques by RECIST v1.1 or PCWG-3 guidelines

You may not qualify if:

• Women who are pregnant, breast feeding, or who plan to become pregnant while in the study or within the protocol defined timeframe after the last administration of study specified treatment.
• Men who plan to father a child while in the study or within the protocol defined timeframe after the last administration of study specified treatment.
• Serious concomitant systemic disorder that would compromise the participants ability to adhere to the protocol including: opportunistic HIV/AIDs-related infection(s) within the past 12 months, hepatitis B virus, or hepatitis C virus; documented active or chronic tuberculosis infection; malignancy prior to the one currently being treated \[including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)\] that is not in remission
• Have MDS/AML or features suggestive of MDS/AML
• Ongoing interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic)
• Moderate or severe cardiovascular disease
• Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment; stable brain metastases are eligible
• Received a live vaccine within 30 days before the first dose of study treatment
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate
• Recent major surgery within 4 weeks prior to entry into the study or minor surgery within 1 week of entry into the study
• Significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment
• Currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
• First-line locally advanced and/or metastatic breast cancer with no prior adjuvant chemotherapy
• Inflammatory breast cancer
• Known hypersensitivity to any of the components of talazoparib

Sponsors & Collaborators

• Artios Pharma Ltd: lead

Study Sites (8)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Florida Cancer Specialists

Orlando, Florida, 32827, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Sarah Cannon Research Institute

London, England, UK/W1G 6AD, United Kingdom

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms

Interventions

talazoparib; niraparib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Erika Hamilton, MD

  Tennessee Oncology

  STUDY CHAIR

• Timothy Yap, MBBS, PhD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: August 5, 2021
• Study Start: September 13, 2021
• Primary Completion: December 24, 2025
• Study Completion: December 24, 2025
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); GB (1)