Talazoparib + Radiotherapy for Small Cell Lung Cancer

Overseen By Benjamin Lok, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must be taking: Platinum agents, Etoposide

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

Disqualifiers: Brain metastases, Myelodysplastic syndrome, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3-4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for small cell lung cancer. Researchers aim to determine if the drug talazoparib (Talzenna), when combined with low-dose radiation, is safe and effective. The primary goal is to identify the highest dose of talazoparib that patients can tolerate without severe side effects. Individuals with small cell lung cancer who have undergone chemotherapy and have not experienced disease progression might be suitable candidates for this trial. 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 new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs like strong P-gp inhibitors or other P-gp and BCRP inhibitors while participating. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that talazoparib is generally well-tolerated when combined with radiotherapy for small cell lung cancer. One study found that patients can safely receive this combination, and it is mostly manageable. The recommended dose for further testing is 1 mg daily. While some side effects might include kidney problems or other serious reactions, these were uncommon. Overall, talazoparib appears promising and safe for use in these situations. Patients should always consult a doctor to understand potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about talazoparib for small cell lung cancer because it offers a unique approach by combining a PARP inhibitor with radiotherapy. Unlike traditional treatments that primarily involve chemotherapy, talazoparib specifically targets the cancer cells' ability to repair DNA damage, potentially making them more vulnerable to radiation. This dual-action approach could enhance the effectiveness of the treatment and reduce the likelihood of cancer cells surviving and spreading. By focusing on this novel mechanism, talazoparib has the potential to improve outcomes for patients with this aggressive form of cancer.

What evidence suggests that talazoparib combined with low dose radiotherapy might be an effective treatment for small cell lung cancer?

This trial will evaluate the combination of Talazoparib with low-dose radiotherapy for small cell lung cancer (SCLC). Research has shown that Talazoparib can enhance the effects of radiation therapy in SCLC. Studies have found that Talazoparib increases cancer cells' sensitivity to radiation, reducing their growth in lab tests. An earlier study demonstrated that using Talazoparib with low-dose radiation therapy was safe for patients, suggesting it might effectively combat SCLC. While more research on humans is needed, these early results are promising for its potential use. ^{1 2 3 4 5}

Who Is on the Research Team?

Benjamin Lok, MD

Principal Investigator

Princess Margaret Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with extensive-stage small cell lung cancer who finished 4-6 cycles of specific chemotherapy without disease progression. They must be able to swallow pills, have good organ function, and not be pregnant or breastfeeding. Excluded are those with untreated brain metastases, prior PARP inhibitor treatment, recent other cancer treatments, serious medical conditions or infections.

Inclusion Criteria

My organs and bone marrow are working well.

I have completed 4-6 cycles of chemotherapy with a platinum agent and etoposide.

I am postmenopausal or not able to bear children, confirmed by a recent negative pregnancy test.

Exclusion Criteria

I have had a bone marrow or cord blood transplant in the past.

I am not taking any drugs that affect drug transport in my body.

I have spinal cord compression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talazoparib starting on day 1 and low dose thoracic radiotherapy starting on day 6-9 for 10 fractions over 2 weeks

3-4 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Follow-up at 3 weeks, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Low Dose Radiotherapy (RT)
• Talazoparib

Trial Overview The study tests the safety of combining talazoparib (a pill) with low dose thoracic radiotherapy in escalating doses to find the highest dose patients can tolerate without severe side effects. Up to 24 patients will start at a lower dose and may increase if it's safe.

How Is the Trial Designed?

Group I: Talazoparib in Combination with Low Dose RT Experimental Treatment 1 Intervention

Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of RT (until day 20-23). Patient will start low dose RT on day 6-9, and will continue for 10 fractions throughout 2 weeks. Talazoparib dose levels will start at 0.5mg daily and increase to 1mg if dose limiting toxicites are not observed. Toxicities include renal impairment and other treatment related toxicities Grade ≥3. Patients will be monitored weekly during study treatment, and followed up at 3 weeks, and every 3 months after for 1 year.

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

Approved in United States as Talzenna for:

• Deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer

Approved in European Union as Talzenna for:

• Monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

PARP inhibition, particularly with the drug talazoparib, significantly sensitizes small cell lung cancer (SCLC) cells to ionizing radiation, as demonstrated in 6 SCLC cell lines and confirmed in patient-derived xenograft models.

Talazoparib's superior PARP trapping activity leads to more double-stranded DNA breaks compared to veliparib, enhancing its effectiveness in combination with radiation therapy, suggesting that PARP inhibitors could improve radiotherapy outcomes for SCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib Is a Potent Radiosensitizer in Small Cell Lung Cancer Cell Lines and Xenografts. Laird, JH., Lok, BH., Ma, J., et al.[2020]

Talazoparib, a PARP inhibitor, showed significant antitumor activity in patients with BRCA1/2 mutations, achieving confirmed responses in 50% of breast cancer patients and 42% of ovarian cancer patients at the recommended dose of 1.0 mg/day.

The treatment was generally well tolerated, with the most common side effects being fatigue and anemia, and a maximum tolerated dose (MTD) established at 1.0 mg/day, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers. de Bono, J., Ramanathan, RK., Mina, L., 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]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

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]

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 EMBRACA trial involving 431 patients with gBRCA1/2-mutated advanced breast cancer, talazoparib did not significantly improve overall survival compared to chemotherapy, with a hazard ratio of 0.848 (P = 0.17).

However, talazoparib showed a significant advantage in improving patient-reported outcomes and delaying deterioration in quality of life and breast symptoms, indicating its potential benefits beyond survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Litton, JK., Hurvitz, SA., Mina, LA., et al.[2023]

A combination of the drugs I-BET762 (a BET inhibitor) and Talazoparib (a PARP inhibitor) showed significant synergy in treating small cell lung cancer (SCLC) cell lines, indicating a promising new strategy for therapy.

This drug synergy was particularly effective in SCLC cells with MYC amplification, and it works by disrupting the DNA damage response process, suggesting that targeting multiple pathways may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BET-Inhibitor I-BET762 and PARP-Inhibitor Talazoparib Synergy in Small Cell Lung Cancer Cells. Fiorentino, FP., Marchesi, I., Schröder, C., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6742772/

Talazoparib is a Potent Radiosensitizer in Small Cell Lung ... Talazoparib radiosensitized 5 of 6 SCLC cell lines in short-term viability assays and confirmed in 3 of 3 cell lines by CSAs.

2. redjournal.org redjournal.org/article/S0360-3016(24)00928-3/fulltext

Phase I Trial of Concurrent Talazoparib and Consolidative ... We aimed to test the hypothesis that combining talazoparib with CTRT is safe in a single institution, open label, single-arm Phase I clinical trial.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03672773

Study Details | NCT03672773 | Talazoparib and Low-Dose ... This phase II trial studies how effective talazoparib and temozolomide are for treating participants with extensive-stage small cell lung cancer.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8517

Primary analysis from the phase 2 study of continuous ... This is a phase 2, open-label, single-arm study of the safety and efficacy of TALA plus TMZ in patients with ES-SCLC, relapsed or refractory to a first-line ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/24/20/5143/258111/Talazoparib-Is-a-Potent-Radiosensitizer-in-Small

Talazoparib Is a Potent Radiosensitizer in Small Cell Lung ... Preliminary results from one trial of patients with relapsed and refractory SCLC reported an objective response rate of 39% for the combination of veliparib and ...