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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well the drug talazoparib works when combined with one of three other drugs—palbociclib, axitinib, or crizotinib—to treat advanced and spreading solid tumors. Talazoparib, a PARP inhibitor, helps stop cancer cells from repairing themselves, potentially preventing their growth. The trial aims to find the best dose and understand the benefits and side effects of these combinations. It might suit people with aggressive solid tumors that have specific genetic changes or those who haven't responded well to standard treatments. Participants should have a solid tumor that is locally advanced or has spread and meets certain genetic criteria.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that talazoparib, when combined with other treatments, might cause serious side effects. It can lead to blood issues such as Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML), affecting the bone marrow.

Studies have found that palbociclib, another drug used in these combinations, can improve cancer treatment outcomes. However, the specific side effects of palbociclib were not detailed in the sources.

When talazoparib is combined with axitinib, specific safety information is unavailable. Axitinib, typically used to treat kidney cancer, carries its own risks and benefits.

Limited information exists on using talazoparib with crizotinib. The FDA has approved talazoparib for treating certain breast cancers, indicating its safety for some conditions. However, each drug combination can have different effects, so it is important to consider these potential risks and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine talazoparib, a PARP inhibitor, with other targeted therapies like palbociclib, axitinib, and crizotinib, each offering a unique approach to tackling advanced cancer. Talazoparib works by hampering the cancer cells' ability to repair DNA, which can lead to cell death, especially when paired with palbociclib, an inhibitor that disrupts cancer cell division, potentially enhancing effectiveness. Meanwhile, the combination with axitinib, which blocks blood vessel growth in tumors, and crizotinib, which targets specific cancer-driving proteins, adds more dimensions to the treatment strategy. Unlike standard options that may focus on chemotherapy or singular pathway inhibition, these combinations offer a multi-faceted assault on cancer cells, possibly leading to better outcomes.

What evidence suggests that this trial's treatments could be effective for advanced cancer?

This trial will evaluate combinations of talazoparib with different drugs for advanced cancer. Research shows that talazoparib, a PARP inhibitor, may prevent cancer cells from repairing themselves, potentially stopping their growth. One arm of the trial will test talazoparib with palbociclib; studies have found that this combination can help patients with certain cancers live longer without disease progression. Another arm will test talazoparib with axitinib, which, when combined with other treatments, has improved survival rates in kidney cancer, suggesting it might also work well with talazoparib. The third arm will test talazoparib with crizotinib, a cancer drug that targets specific growth enzymes and has been effective in certain cancers. Although data on these combinations with talazoparib is limited, early signs are promising for controlling advanced solid tumors. ^{1 2 3 4 5}

Who Is on the Research Team?

Timothy Yap

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

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Talzenna (talazoparib) News Talazoparib plus enzalutamide resulted in statistically significant and clinically meaningful improvement in survival versus enzalutamide plus placebo, further ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40158923/

A Phase 1b/2 Study of Talazoparib and Axitinib in Patients ... In this phase 1b/2 study, we assessed the safety and antitumor activity of axitinib combined with talazoparib in treatment-refractory clear-cell renal cell ...

3. withpower.com withpower.com/trial/phase-2-carcinoma-3-2020-b6b22

Talazoparib + Axitinib for Advanced Kidney Cancer Research shows that axitinib, when combined with pembrolizumab, has improved outcomes in advanced kidney cancer, including better survival rates and response ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04693468

NCT04693468 | Talazoparib and Palbociclib, Axitinib, or ... Giving talazoparib in combination with palbociclib, axitinib, or crizotinib may help control locally advanced or metastatic solid tumors. Detailed Description.

5. inlyta.com inlyta.com/axitinib/clinical-trial-results

INLYTA® (axitinib) Clinical Trial Results | Safety Info Patients taking INLYTA experienced a median PFS of 6.7 months compared with 4.7 months for those taking Nexavar. That's a 2-month increase in median PFS.