Atezolizumab + Talazoparib for Small Cell Lung Cancer

Recruiting at 661 trial locations

Overseen By Raid Aljumaily

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum, Etoposide, Atezolizumab

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

Disqualifiers: Brain metastases, Uncontrolled diabetes, Active tuberculosis, 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

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

Compensation: Varies

Number of Visits: 22

Duration: 21-day cycles, repeated

94 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies whether atezolizumab in combination with talazoparib works better than atezolizumab alone as maintenance therapy for patients with SLFN11-positive extensive-stage small cell lung cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PARPs are proteins that help repair damage to DNA, the genetic material that serves as the body's instruction book. Changes (mutations) in DNA can cause tumor cells to grow quickly and out of control, but PARP inhibitors like talazoparib may keep PARP from working, so tumor cells can't repair themselves, and they stop growing. Giving atezolizumab in combination with talazoparib may help lower the chance of extensive-stage small cell lung cancer growing and spreading compared to atezolizumab alone.

Will I have to stop taking my current medications?

The trial requires that participants do not take certain medications, such as strong P-glycoprotein inhibitors, P-glycoprotein inducers, or breast cancer resistance protein inhibitors, within 7 days before starting the trial and during the trial. If you are taking these medications, you may need to stop them.

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

Atezolizumab, when combined with chemotherapy, has been shown to improve survival in patients with extensive-stage small cell lung cancer. Talazoparib is effective in treating certain types of breast cancer, and it is being explored for use in other cancers, suggesting potential benefits when combined with Atezolizumab. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Talazoparib safe for humans?

Atezolizumab has been studied for safety in patients with small-cell lung cancer and non-small-cell lung cancer, showing it can be safely used in humans. Talazoparib has also shown promising safety results in patients with advanced breast cancer. ^{2 3 5 6 7}

How is the drug combination of Atezolizumab and Talazoparib unique for treating small cell lung cancer?

The combination of Atezolizumab and Talazoparib is unique because Atezolizumab is a PD-L1 inhibitor that helps the immune system attack cancer cells, while Talazoparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, making this a novel approach for treating small cell lung cancer. ^{2 3 4 7 8}

Research Team

Nagla Abdel Karim

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with extensive-stage small cell lung cancer (ES-SCLC) confirmed by biopsy, who have completed initial treatment without disease progression or severe immune-related side effects. They must not have mixed SCLC/NSCLC histology, active pneumonitis, uncontrolled diseases like diabetes or infections, and no prior immunotherapy for SCLC. Participants need adequate organ function and cannot be pregnant or breastfeeding.

Inclusion Criteria

My kidney function, measured by creatinine levels or clearance, is within the normal range.

Participants must not be pregnant due to the potential teratogenic side effects of the protocol treatment. Women of reproductive potential and men must have agreed to use an effective contraception method for the duration of protocol treatment, and for 7 months after the last dose of protocol treatment. A woman is considered to be of "reproductive potential" if she has had a menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding must be discontinued prior to Step 2 Randomization

I am 18 years old or older.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive atezolizumab alone or in combination with talazoparib as maintenance therapy

21-day cycles, repeated

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Regular visits (in-person)

Long-term follow-up

Participants are monitored for overall survival

Up to 3 years

Treatment Details

Interventions

• Atezolizumab
• Talazoparib

Trial Overview The study tests if atezolizumab combined with talazoparib improves outcomes in ES-SCLC patients with the SLFN11 biomarker compared to atezolizumab alone. Atezolizumab is an antibody that may boost the immune system's response to cancer; talazoparib inhibits PARP proteins involved in DNA repair in tumor cells.

Participant Groups

Group I: Arm II (atezolizumab, talazoparib) Experimental Treatment 6 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1 and talazoparib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.

Group II: Arm I (atezolizumab) Active Control 5 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo MRI during screening. Patients undergo tumor biopsy while on study. Patients undergo CT scan and blood sample collection throughout the study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The combination of the anti-PD-1 antibody budigalimab and the antibody-drug conjugate Rova-T was found to be tolerated in 31 patients with previously treated small cell lung cancer (SCLC), with common side effects including pleural effusion, fatigue, and cough.

This combination therapy showed an overall response rate of 24.1%, with one complete response and six partial responses, indicating promising efficacy despite the discontinuation of Rova-T's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Calvo, E., Spira, A., Miguel, M., et al.[2022]

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 phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

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 a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

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

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]

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

Talazoparib: First Global Approval. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

7. 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]

8. England 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. [2023]