What side effects are associated with this type of intervention?

Common treatments for breast cancer involving PARP inhibitors, such as talazoparib, often include side effects like anemia, nausea, fatigue, and thrombocytopenia. These treatments can also cause neutropenia and gastrointestinal issues. When combined with other agents, such as in the ART4215 trial, additional side effects may include asthenia and anorexia. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several PARP inhibitors for the treatment of breast cancer, particularly for patients with BRCA mutations. Olaparib (Lynparza) was one of the first PARP inhibitors approved for metastatic breast cancer with germline BRCA mutations. Talazoparib (Talzenna) is another PARP inhibitor approved for similar indications. These drugs work by exploiting the DNA repair weaknesses in cancer cells with BRCA mutations, leading to cell death. Additionally, niraparib (Zejula) has shown activity in clinical trials for breast cancer and is being studied further. These treatments are particularly relevant for patients with homologous recombination repair deficiencies.

What other types of research exist?

Promising alternatives to ART4215 for breast cancer patients include olaparib and talazoparib, both of which are PARP inhibitors. Additionally, combination therapies such as abiraterone plus olaparib have shown efficacy in clinical trials. Other novel options include trastuzumab deruxtecan for HER2-low advanced breast cancer and pembrolizumab for patients with high tumor mutational burden.

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ART4215 for Advanced Cancer

Q: What is the mechanism of action of this treatment?

PARP inhibitors, such as olaparib and talazoparib, work by inhibiting the PARP enzyme, which is essential for repairing single-strand DNA breaks. This leads to the accumulation of DNA damage in cancer cells, particularly those with BRCA1/2 mutations, causing cell death. Combining PARP inhibitors with other agents, like talazoparib or niraparib, can enhance this effect by further disrupting DNA repair or adding cytotoxic stress. This targeted approach is crucial for breast cancer patients as it can improve treatment efficacy and reduce side effects compared to traditional chemotherapy.

Phase 1

Waitlist Available

Research Sponsored by Artios Pharma Ltd

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Additional inclusion criteria for participants in dose expansion (Part B3): HER2-negative locally advanced or metastatic breast cancer. Deleterious or suspected deleterious germline or somatic BRCA1 or BRCA2 mutation. No more than 3 prior chemotherapy-inclusive regimens (including antibody conjugates). Prior treatment with a taxane or anthracycline unless contraindicated. No or </= 1 month of prior treatment with a PARP inhibitor. At least 1 measurable lesion assessable using standard techniques by RECIST v1.1. Non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available for submission for analysis

At least 1 radiologically evaluable lesion that can be assessed at baseline and is suitable for repeated radiological evaluation by RECIST v1.1 or Prostate Cancer Working Group-3 for patients with prostate cancer

Must not have

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

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the first dose until up to 30 days after the last dose of art4215. each cycle is 21 days.

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ART4215, an experimental oral drug, in patients with advanced cancers. It works by blocking an enzyme that helps cancer cells repair their DNA, potentially stopping their growth. The study aims to find a safe dose and understand its side effects and effectiveness.

Who is the study for?

This trial is for adults with advanced or metastatic solid tumors suitable for PARP inhibitor treatment. Eligible participants may have had prior chemotherapy but not more than three regimens, and no previous PARP inhibitors unless specified. They must have at least one measurable tumor lesion, adequate organ function, and agree to use effective contraception.

What is being tested?

ART4215 is being tested alone and alongside talazoparib or niraparib in patients with various cancers including breast cancer. The study aims to determine the safe dosage levels, side effects profile, and effectiveness of these treatments in combating cancer progression.

What are the potential side effects?

Potential side effects include reactions related to drug infusion, fatigue, digestive issues like nausea or constipation, blood cell count changes increasing infection risk, liver or kidney function alterations. Specific side effect profiles will be studied during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have at least one tumor that can be seen and measured on scans.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

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I plan to try for a child during or soon after the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the first dose until up to 30 days after the last dose of art4215. each cycle is 21 days.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the first dose until up to 30 days after the last dose of art4215. each cycle is 21 days.

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the first dose until up to 30 days after the last dose of art4215. each cycle is 21 days. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

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

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

Secondary study objectives

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

Change in tumor size as a measure of efficacy for ART4215 as monotherapy, in combination with talazoparib or in combination with niraparib

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

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Part B3Experimental Treatment2 Interventions

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.

Group II: Part B2Experimental Treatment1 Intervention

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

Group III: Part B1Experimental Treatment1 Intervention

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.

Group IV: Part A3Experimental Treatment2 Interventions

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.

Group V: Part A2Experimental Treatment2 Interventions

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.

Group VI: Part A1Experimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Niraparib

2018

Completed Phase 4

~2400

Talazoparib

2021

Completed Phase 2

~2820

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

PARP inhibitors, such as olaparib and talazoparib, work by inhibiting the PARP enzyme, which is essential for repairing single-strand DNA breaks. This leads to the accumulation of DNA damage in cancer cells, particularly those with BRCA1/2 mutations, causing cell death. Combining PARP inhibitors with other agents, like talazoparib or niraparib, can enhance this effect by further disrupting DNA repair or adding cytotoxic stress. This targeted approach is crucial for breast cancer patients as it can improve treatment efficacy and reduce side effects compared to traditional chemotherapy.

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.