Triple Therapy for Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Atezolizumab

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Brain metastases, Cardiac disorder, others

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

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

Compensation: Varies

Number of Visits: 14

74 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib/II trial studies the best dose of temozolomide and how well it works with niraparib and atezolizumab in treating patients with solid tumors that have spread to other places in the body (advanced) and extensive-stage small cell lung cancer with a complete or partial response to platinum-based first-line chemotherapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. 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. Giving temozolomide, niraparib and atezolizumab may work better in treating patients with advanced solid tumors and extensive-stage small cell lung cancer.

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 must not have used antineoplastic therapies or any other investigational agent within 21 days before starting the study treatment. Also, you should already be receiving atezolizumab infusions and continue them while on trial. It's best to discuss your current medications with the trial team to ensure eligibility.

What data supports the idea that Triple Therapy for Small Cell Lung Cancer is an effective treatment?

The available research shows that combining atezolizumab with chemotherapy improves survival for patients with extensive-stage small cell lung cancer compared to chemotherapy alone. This suggests that the Triple Therapy, which includes atezolizumab, could be more effective than other treatments that do not include this drug. ^{1 2 3 4 5}

What safety data is available for the triple therapy treatment for small cell lung cancer?

The safety data for atezolizumab, a component of the triple therapy, shows it has an acceptable safety profile based on clinical trials for various cancers, including non-small cell lung cancer. Common adverse reactions include fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation. Grade 3 to 4 adverse events include dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, and liver enzyme increases. Immune-related adverse events include pneumonitis, hepatitis, colitis, and thyroid disease, each occurring in about 1.4% of patients. The safety profile of niraparib and temozolomide, other components of the therapy, is not detailed in the provided research. ^{1 2 6 7 8}

Is the drug combination Atezolizumab, Niraparib, and Temozolomide promising for small cell lung cancer?

Yes, the drug combination shows promise for small cell lung cancer. Atezolizumab has shown positive results in cancer treatments, and Temozolomide has demonstrated substantial clinical activity in small cell lung cancer when combined with other drugs. This suggests that the combination could be a promising new strategy for treating this type of cancer. ^{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 advanced solid tumors or extensive-stage small cell lung cancer who've responded to first-line platinum chemotherapy. They must be in good physical condition, not pregnant, willing to use contraception, and have no serious health issues or recent cancer treatments. Certain blood counts and organ functions are required.

Inclusion Criteria

I will use a condom with partners who are pregnant or can become pregnant.

I've had a good response to platinum-based chemotherapy after 4-6 cycles.

Participants must agree not to donate sperm or eggs, not to breastfeed, and not to donate blood

Exclusion Criteria

Use of any other investigational agent within 21 days before day 1 of study treatment

I do not have serious health issues or recent major surgeries that could affect my participation.

I still experience side effects from past treatments, except for hair loss or acceptable lab results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Finding and Treatment (Phase Ib)

Determine the recommended phase II dose (RP2D) of temozolomide in combination with niraparib and atezolizumab. Patients receive temozolomide orally once daily on days 1-5 and niraparib orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive atezolizumab intravenously every 3 weeks.

28 days per cycle

Every 3 weeks (in-person)

Maintenance Therapy (Phase II)

Evaluate the efficacy of niraparib plus temozolomide plus atezolizumab at RP2D compared with atezolizumab alone. Patients continue to receive treatments as per their assigned arm.

Up to 36 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs at 30 days post-treatment, then every 8 weeks for 24 weeks, and every 12 weeks for up to 1 year.

Up to 1 year

Every 8-12 weeks (in-person)

Treatment Details

Interventions

• Atezolizumab
• Niraparib
• Temozolomide

Trial Overview The study tests the combination of temozolomide (a chemo drug), niraparib (a PARP inhibitor that blocks DNA repair in cancer cells), and atezolizumab (an immunotherapy). It aims to find the best dose and see if this mix is more effective for patients with certain advanced cancers.

Participant Groups

Group I: Arm A (temozolomide, niraparib, atezolizumab) Experimental Treatment 5 Interventions

Patients receive temozolomide PO QD on days 1-5 and niraparib PO QD on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care atezolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (atezolizumab) Active Control 3 Interventions

Patients receive standard of care atezolizumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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+

Translational Research in Oncology-U.S

Collaborator

Trials

2

Recruited

160+

Tesaro, Inc.

Industry Sponsor

Trials

57

Recruited

10,600+

Findings from Research

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

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]

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]

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]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., 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]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

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]

Immunotherapy, particularly with pembrolizumab or atezolizumab combined with platinum-based chemotherapy, has become an effective first-line treatment for advanced non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels.

Patients with negative PD-L1 expression and low tumor mutational burden (TMB) may not benefit from immunotherapy combinations and might be better treated with traditional platinum-based chemotherapy, highlighting the need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. Proto, C., Ferrara, R., Signorelli, D., et al.[2019]

References

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

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

Atezolizumab: First Global Approval. [2019]

3. 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]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

5. 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]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

7. 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]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

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

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. [2019]