Atezolizumab + Tiragolumab for Squamous Cell Carcinoma

Overseen By Emma Holliday, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunotherapy, Chemotherapy, Corticosteroids, others

Disqualifiers: Autoimmune disease, Cardiovascular disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

55 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on active cancer therapy or certain immunosuppressive medications before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Atezolizumab and Talazoparib for treating Squamous Cell Carcinoma?

Atezolizumab has been shown to improve survival in patients with small cell lung cancer and has demonstrated activity in non-small cell lung cancer, suggesting its potential effectiveness in other cancers. Talazoparib has been effective in prolonging progression-free survival in breast cancer patients with specific genetic mutations, indicating its potential benefit in cancer treatment. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Tiragolumab safe for humans?

Atezolizumab has been studied for safety in various cancers, including lung, ovarian, and uterine cancers, and has shown to be generally safe in these contexts. Talazoparib has also shown promising safety in patients with advanced breast cancer. ^{2 6 7 8 9}

How is the drug combination of Atezolizumab and Talazoparib unique for treating squamous cell carcinoma?

This treatment is unique because it combines Atezolizumab, which boosts the immune system to fight cancer, with Talazoparib, a drug that targets cancer cells with specific genetic mutations, potentially offering a novel approach for squamous cell carcinoma compared to traditional chemotherapy. ^{2 3 5 6 10}

What is the purpose of this trial?

A single-arm, phase II study for patients with detectable HPV CtDNA at 12 weeks or longer after completion of definitive therapy for non-metastatic, HPV+ squamous cell carcinoma.

Research Team

Emma Holliday, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for individuals who have completed treatment for non-metastatic, HPV-positive squamous cell carcinoma and still show detectable HPV ctDNA after 12 weeks or more. Specific eligibility details are not provided.

Inclusion Criteria

I do not have active hepatitis C.

I agree to avoid fathering a child or will use contraception.

My blood and organ tests meet the required health standards.

Exclusion Criteria

I have previously been treated with CD137 agonists or experimental immune therapies.

I am a woman who can have children and have a recent negative pregnancy test.

I have not received a live vaccine in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab and tiragolumab for detectable HPV ctDNA after definitive therapy for HPV+ squamous cell carcinoma

12 weeks

Outpatient basis

Follow-up

Participants are monitored for safety, toxicity, and disease-free survival

1 year

Treatment Details

Interventions

• Atezolizumab
• Talazoparib

Trial Overview The study is testing the effectiveness of Atezolizumab and Tiragolumab in patients with persistent HPV ctDNA following definitive therapy for their cancer. It's a phase II trial where all participants receive the same treatments.

Participant Groups

Group I: Atezolizumab + Tiragolumab Experimental Treatment 2 Interventions

Treatment will be administered on an outpatient basis

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Strategic Alliance

Collaborator

Trials

2

Recruited

90+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

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]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

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 a study of 18 advanced non-small cell lung cancer patients, re-treatment with the anti-PD-L1 antibody atezolizumab after anti-PD-1 therapy showed limited efficacy, with a median progression-free survival of only 2.9 months and no patients achieving a partial or complete response.

The safety profile of atezolizumab was comparable to that of the previous anti-PD-1 treatments, as there were no significant differences in immune-related adverse events between the two therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment With Anti-PD-L1 Antibody in Advanced Non-small Cell Lung Cancer Previously Treated With Anti-PD-1 Antibodies. Fujita, K., Uchida, N., Yamamoto, Y., et al.[2019]

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]

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]

Atezolizumab, a PD-L1 inhibitor, was well tolerated in patients with advanced ovarian and uterine cancers, with no new safety concerns and mostly mild treatment-related adverse events.

Preliminary results showed anti-tumor activity in some patients, with long durations of response, suggesting that atezolizumab may be a promising treatment option for these cancers, especially in those with high microsatellite instability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. Liu, JF., Gordon, M., Veneris, J., et al.[2019]

Anti-PD-1/PD-L1 therapies (atezolizumab, pembrolizumab, nivolumab) significantly improve overall survival and progression-free survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC) compared to docetaxel, based on a review of 14 trials involving 3786 subjects.

For patients with EGFR wild-type NSCLC, anti-PD-1/PD-L1 therapy offers better survival outcomes than EGFR-TKIs, while for EGFR mutant patients, it is less effective than EGFR-TKIs in terms of progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. Sheng, Z., Zhu, X., Sun, Y., et al.[2021]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

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]

References

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

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

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

3. 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]

4. Greece pubmed.ncbi.nlm.nih.gov

Retreatment With Anti-PD-L1 Antibody in Advanced Non-small Cell Lung Cancer Previously Treated With Anti-PD-1 Antibodies. [2019]

5. 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]

6. 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]

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

Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. [2019]

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

The efficacy of anti-PD-1/PD-L1 therapy and its comparison with EGFR-TKIs for advanced non-small-cell lung cancer. [2021]

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

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. [2020]

10. 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]