Talazoparib + Temozolomide for Small Cell Lung Cancer

Recruiting at 5 trial locations

Overseen By TRIO-US IST Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: PARP inhibitors

Disqualifiers: Myelodysplastic syndrome, Gastrointestinal disorder, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how effective talazoparib and temozolomide are for treating patients with extensive-stage small cell lung cancer that has come back after initial chemotherapy. Talazoparib stops cancer cells from repairing their DNA, while temozolomide kills or stops the growth of these cells. The combination may work better than either drug alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use certain drugs like P-gp inhibitors or inducers and BCRP inhibitors. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination Talazoparib and Temozolomide for Small Cell Lung Cancer?

Research shows that a similar drug combination, olaparib and temozolomide, had a 41.7% response rate in patients with relapsed small-cell lung cancer, suggesting a promising new strategy for this difficult-to-treat cancer. ^{1 2 3 4 5}

Is the combination of Talazoparib and Temozolomide safe for humans?

The combination of Talazoparib and Temozolomide has shown toxicity in both preclinical and clinical testing, requiring a reduction in the dose of Temozolomide when used with oral Talazoparib. However, a new nanoparticle formulation of Talazoparib has been developed that reduces toxicity and allows for higher doses without reducing Temozolomide, suggesting improved safety. ^{1 2 6 7 8}

What makes the drug combination of Talazoparib and Temozolomide unique for treating small cell lung cancer?

The combination of Talazoparib and Temozolomide is unique because Talazoparib is a PARP inhibitor that enhances the effectiveness of Temozolomide, a chemotherapy drug, by preventing cancer cells from repairing their DNA. This combination is being explored for small cell lung cancer, where effective treatment options are limited, and it may offer a new approach by potentially reducing toxicity when using a nanoparticle formulation of Talazoparib. ^{1 2 3 9 10}

Research Team

Jonathan W. Goldman

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with extensive-stage small cell lung cancer that has returned after initial chemotherapy. Participants must be able to swallow pills, not have used PARP inhibitors or temozolomide before, and agree to contraception. They should not have other cancers within the last 2 years (with some exceptions) or conditions affecting study participation.

Inclusion Criteria

I agree not to donate sperm or eggs during and up to 105/45 days after my treatment.

I am capable of understanding and agreeing to the trial's terms.

My blood clotting time is normal or managed if I'm on blood thinners.

Exclusion Criteria

I have recovered from previous treatment side effects, except for hair loss or acceptable lab results.

I haven't had another cancer, except certain types, in the last 2 years.

My cancer worsened after initial strong chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive temozolomide orally on days 1-5 and talazoparib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then up to 1 year.

Up to 1 year

Treatment Details

Interventions

• Talazoparib
• Temozolomide

Trial Overview The effectiveness of talazoparib combined with low-dose temozolomide is being tested in participants with relapsed or refractory extensive-stage small cell lung cancer. Talazoparib may prevent tumor cells from repairing DNA, while temozolomide aims to stop their growth.

Participant Groups

Group I: Treatment (temozolomide, talazoparib) Experimental Treatment 2 Interventions

Participants receive temozolomide PO on days 1-5 and talazoparib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Translational Research in Oncology

Collaborator

Trials

22

Recruited

6,700+

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

Findings from Research

The nanoparticle formulation of talazoparib (NanoTLZ) significantly reduced toxicity compared to the oral form of talazoparib when combined with temozolomide (TMZ), allowing for a higher maximum tolerated dose.

Using NanoTLZ with TMZ did not require a dose reduction of TMZ, which was necessary when using oral talazoparib, suggesting that this delivery method may enhance the safety and efficacy of the treatment for Ewing sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanoformulation of Talazoparib Increases Maximum Tolerated Doses in Combination With Temozolomide for Treatment of Ewing Sarcoma. Baldwin, P., Likhotvorik, R., Baig, N., et al.[2020]

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]

Temozolomide combined with olaparib shows promise as a treatment option for patients with small-cell lung cancer who have progressive disease after standard etoposide and platinum-based therapy.

The study emphasizes the use of co-clinical trials with patient-derived xenografts to enhance biomarker discovery, potentially leading to more personalized and effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide plus PARP Inhibition in Small-Cell Lung Cancer: Could Patient-Derived Xenografts Accelerate Discovery of Biomarker Candidates? Pacheco, JM., Byers, LA.[2019]

The combination of olaparib and temozolomide showed a promising overall response rate of 41.7% in a phase I/II trial involving 50 patients with previously treated small-cell lung cancer (SCLC), indicating its potential as an effective treatment option.

A molecular signature was identified that correlates low expression of inflammatory-response genes with resistance to the treatment, helping to predict which tumors are more likely to respond to the olaparib/temozolomide combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. Farago, AF., Yeap, BY., Stanzione, M., et al.[2020]

In a phase II study involving 69 patients with limited-stage small-cell lung cancer, the combination of tirapazamine with chemoradiotherapy resulted in a median overall survival of 21 months, which aligns with previous promising results from an earlier pilot study.

Despite some significant toxicities, including grade 3 to 4 esophagitis in 25% of patients, the study demonstrated acceptable safety levels, suggesting that further research into hypoxia-targeted therapies like tirapazamine is justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of tirapazamine, cisplatin, and etoposide and concurrent thoracic radiotherapy for limited-stage small-cell lung cancer: SWOG 0222. Le, QT., Moon, J., Redman, M., et al.[2023]

Talazoparib, a PARP inhibitor used for breast cancer, shows potential as an effective modulator of multidrug resistance (MDR) by reversing resistance to other chemotherapy drugs like daunorubicin and mitoxantrone in cancer cells expressing specific transporters (ABCC1 and ABCG2).

The study found that talazoparib has minimal impact on the activity of key cytochrome P450 enzymes and does not significantly affect the expression of MDR-related transporters, suggesting a favorable safety profile regarding drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talazoparib Does Not Interact with ABCB1 Transporter or Cytochrome P450s, but Modulates Multidrug Resistance Mediated by ABCC1 and ABCG2: An in Vitro and Ex Vivo Study. Sabet, Z., Vagiannis, D., Budagaga, Y., et al.[2022]

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]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

In a real-world study of 84 patients with germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer, talazoparib showed a median progression-free survival of 8.7 months and an overall response rate of 63.1%, indicating its efficacy in this population.

The study found that factors such as brain metastasis and a poor performance status (ECOG PS ≥2) at the start of talazoparib treatment were linked to worse outcomes, highlighting the importance of patient characteristics in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics, Treatment, and Outcomes of Real-World Talazoparib-Treated Patients With Germline BRCA-Mutated Advanced HER2-Negative Breast Cancer. Savill, KMZ., Ivanova, J., Asgarisabet, P., et al.[2023]

A phase I trial involving 41 pediatric patients with recurrent or refractory solid tumors showed that the combination of talazoparib and irinotecan, with or without temozolomide, is feasible and has demonstrated activity, particularly in Ewing sarcoma, with objective response rates of 10.3% for arm A and 25% for arm B.

The most common severe side effects included neutropenia and thrombocytopenia, indicating that while the treatment is active, it also carries significant hematologic risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies. Federico, SM., Pappo, AS., Sahr, N., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Nanoformulation of Talazoparib Increases Maximum Tolerated Doses in Combination With Temozolomide for Treatment of Ewing Sarcoma. [2020]

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

Talazoparib: First Global Approval. [2020]

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

Temozolomide plus PARP Inhibition in Small-Cell Lung Cancer: Could Patient-Derived Xenografts Accelerate Discovery of Biomarker Candidates? [2019]

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

Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. [2020]

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

Phase II study of tirapazamine, cisplatin, and etoposide and concurrent thoracic radiotherapy for limited-stage small-cell lung cancer: SWOG 0222. [2023]

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

Talazoparib Does Not Interact with ABCB1 Transporter or Cytochrome P450s, but Modulates Multidrug Resistance Mediated by ABCC1 and ABCG2: An in Vitro and Ex Vivo Study. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Characteristics, Treatment, and Outcomes of Real-World Talazoparib-Treated Patients With Germline BRCA-Mutated Advanced HER2-Negative Breast Cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A phase I trial of talazoparib and irinotecan with and without temozolomide in children and young adults with recurrent or refractory solid malignancies. [2021]