Talazoparib Combinations for Advanced Cancer

Overseen By Timothy Yap

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: P-gp inhibitors, CYP3A4 inhibitors

Disqualifiers: MDS, Brain metastases, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 40

Duration: Up to 2 years

111 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of drugs to treat patients with advanced solid tumors. The treatment aims to find the best dose and understand the benefits and side effects. It works by stopping tumor cells from repairing and growing.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain medications like potent P-gp inhibitors or strong CYP3A4 inhibitors and inducers close to the time of enrollment. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Talazoparib in treating advanced cancer?

Talazoparib has shown effectiveness in treating advanced breast cancer, particularly in patients with specific genetic mutations (BRCA1/2), by improving progression-free survival and quality of life compared to traditional chemotherapy. ^{1 2 3 4 5}

Is Talazoparib safe for humans?

Talazoparib has shown a manageable safety profile in patients with advanced breast cancer and prostate cancer, indicating it is generally safe for humans. ^{1 2 5 6 7}

What makes the drug combination of Talazoparib, Axitinib, Crizotinib, and Palbociclib unique for advanced cancer?

This drug combination is unique because it includes Talazoparib, an oral PARP inhibitor that targets cancer cells with specific genetic mutations (BRCA mutations), potentially offering a more targeted approach compared to traditional chemotherapy. Talazoparib has shown promising results in improving quality of life and prolonging survival in patients with certain types of breast cancer, and its combination with other drugs may enhance its effectiveness in treating advanced cancers. ^{1 2 5 8 9}

Research Team

Timothy Yap

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors who can swallow pills, have no allergies to study drugs, and are not pregnant. They must have specific gene defects related to cancer growth or DNA repair, adequate blood counts and organ function, and a performance status that allows daily activity. Patients with recent treatments or surgeries, uncontrolled infections like hepatitis B/C or HIV, brain metastases needing steroids, other recent malignancies (except prostate cancer in some cases), or those on strong CYP3A4 inhibitors/inducers cannot join.

Inclusion Criteria

Total serum bilirubin =< 1.5 x ULN

I am fully active or can carry out light work.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I do not have any severe medical or mental health issues currently.

I have not had cancer treatment or radiation in the last 2 weeks.

You cannot have participated in any other clinical trial involving new or experimental drugs within 4 weeks before enrolling in this study or during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talazoparib in combination with either palbociclib, axitinib, or crizotinib. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 12 weeks until disease progression, receipt of another cancer drug, or for another two years.

Up to 2 years

Every 12 weeks

Treatment Details

Interventions

• Axitinib
• Crizotinib
• Palbociclib
• Talazoparib

Trial Overview The TalaCom Trial is testing the combination of talazoparib (a PARP inhibitor that prevents tumor cells from repairing their DNA) with either palbociclib, axitinib, or crizotinib (drugs that block enzymes needed for cell growth). The goal is to determine the best dose and see if this combo can control tumor growth better than current treatments.

Participant Groups

Group I: Arm III (talazoparib, crizotinib) Experimental Treatment 2 Interventions

Patients receive talazoparib PO QD on days 1-28 and crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

Group II: Arm II (talazoparib, axitinib) Experimental Treatment 2 Interventions

Patients receive talazoparib PO QD on days 1-28 and axitinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

Group III: Arm I (talazoparib, palbociclib) Experimental Treatment 2 Interventions

Patients receive talazoparib PO QD on days 1-21 or 1-28 and palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient may continue treatment even if there is progression of disease as long as the patient remains clinically stable, per the treating physician's discretion.

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 20 patients with operable BRCA-positive breast cancer, talazoparib treatment for 6 months resulted in a 53% rate of complete pathologic response (RCB-0) and a 63% rate of minimal residual disease (RCB-0/I), indicating significant efficacy without chemotherapy.

While talazoparib was effective, it also caused manageable side effects, with 40% of patients experiencing grade 3 anemia and requiring transfusions, highlighting the importance of monitoring and managing toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. Litton, JK., Scoggins, ME., Hess, KR., et al.[2021]

In the ABRAZO study, talazoparib (1 mg/day) maintained global health status and quality of life (GHS/QoL) in patients with advanced breast cancer, with median time to deterioration of GHS/QoL being 2.8 months for those with prior platinum therapy and 5.5 months for those with multiple cytotoxic regimens.

Patients reported significant improvements in breast and arm symptoms, as well as their future perspective, despite some deterioration in role functioning and dyspnoea symptoms, indicating that talazoparib can provide meaningful benefits in symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial. Hurvitz, SA., Quek, RGW., Turner, NC., et al.[2021]

In a study involving 136 patients with gBRCA1/2 mutated HER2-positive advanced breast cancer, talazoparib did not show a significant improvement in disease-free survival (DFS) or overall survival (OS) compared to conventional chemotherapy after a median follow-up of 70.9 months.

The results suggest that talazoparib is not more effective than standard chemotherapy for this patient population, indicating that treatment decisions should consider this lack of difference in outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between talazoparib and conventional chemotherapy in the treatment of HER2-positive breast cancer patients: A retrospective study. Wang, N., Yu, X.[2022]

The combination of the AKT inhibitor ipatasertib with paclitaxel significantly improved progression-free survival in patients with metastatic triple-negative breast cancer, especially in those with specific genetic alterations (PIK3CA/AKT1/PTEN).

Circulating tumor DNA (ctDNA) analysis showed that lower levels of ctDNA during treatment were associated with better outcomes, indicating that ctDNA could be a useful tool for monitoring treatment response and prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer. Wongchenko, MJ., Kim, SB., Saura, C., et al.[2022]

In a phase III trial, talazoparib, a PARP inhibitor, showed promising results for patients with advanced or metastatic HER2-negative breast cancer and BRCA1/2 mutations, leading to some complete responses and prolonged progression-free survival.

Patients treated with talazoparib also experienced improved overall quality of life compared to those receiving chemotherapy, highlighting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib Bests Chemo for Breast Cancer. [2019]

In the TALAPRO-1 study involving 97 men with metastatic castration-resistant prostate cancer (mCRPC), talazoparib significantly improved health-related quality of life (HRQoL) and reduced pain levels, particularly in patients with BRCA1/2 mutations.

The study found that 84% of all patients and 83% of those with BRCA1/2 mutations did not experience a deterioration in worst pain after 12 months of treatment, indicating a high probability of maintaining pain relief while receiving talazoparib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1. Saad, F., de Bono, J., Barthélémy, P., et al.[2023]

In a phase I study involving 38 patients with advanced solid tumors, talazoparib showed no significant impact of hepatic impairment on its pharmacokinetics, meaning the drug's clearance from the body was not affected by liver function.

Talazoparib was well tolerated, and its safety profile was consistent with previous findings, leading to the conclusion that no dose adjustments are necessary for patients with varying degrees of hepatic impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pharmacokinetics and safety of talazoparib in patients with advanced cancer and varying degrees of hepatic impairment. Guo, C., Yu, Y., Chakrabarti, J., et al.[2022]

Talazoparib is an oral PARP inhibitor recently approved in the USA for treating adults with specific types of breast cancer, particularly those with BRCA mutations, highlighting its targeted efficacy in a defined patient population.

The drug is also being explored for use in other cancers, including metastatic castration-resistant prostate cancer and early triple negative breast cancer, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib: First Global Approval. Hoy, SM.[2020]

Talazoparib tosylate is an FDA and EMA-approved oral PARP inhibitor specifically effective for treating breast cancer in patients with germline BRCA mutations, showing superior efficacy compared to other PARP inhibitors and standard chemotherapy.

The drug works through a mechanism called synthetic lethality, which means it targets cancer cells' weaknesses, providing significant clinical benefits for patients with advanced or metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib to treat BRCA-positive breast cancer. Guney Eskiler, G.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant Talazoparib for Patients With Operable Breast Cancer With a Germline BRCA Pathogenic Variant. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison between talazoparib and conventional chemotherapy in the treatment of HER2-positive breast cancer patients: A retrospective study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Talazoparib Bests Chemo for Breast Cancer. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Patient-reported Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Harboring DNA Damage Response Alterations Treated with Talazoparib: Results from TALAPRO-1. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of pharmacokinetics and safety of talazoparib in patients with advanced cancer and varying degrees of hepatic impairment. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Talazoparib: First Global Approval. [2020]

9. Spain pubmed.ncbi.nlm.nih.gov

Talazoparib to treat BRCA-positive breast cancer. [2019]