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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three treatments—temozolomide, niraparib, and atezolizumab—to determine their effectiveness against advanced solid tumors and extensive-stage small cell lung cancer. Temozolomide is a chemotherapy drug that stops cancer cells from growing, niraparib is a targeted therapy that prevents cancer cells from repairing damaged DNA, and atezolizumab is an immunotherapy that enhances the immune system to fight cancer. Participants with small cell lung cancer who responded positively to earlier chemotherapy might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of temozolomide, niraparib, and atezolizumab is under study for its potential benefits in treating advanced solid tumors and small cell lung cancer. This combination has shown promise in extending the time before cancer worsens, known as improving progression-free survival.

Regarding safety, these treatments have been used before, both alone and in different combinations. Temozolomide is a chemotherapy drug, niraparib is a PARP inhibitor (a targeted therapy that stops cancer cells from repairing themselves), and atezolizumab is an immunotherapy drug that helps the immune system fight cancer. Previous studies have generally found these drugs to be well-tolerated, though they can cause side effects. Common side effects include tiredness, nausea, and low blood cell counts. Serious side effects are less common but can occur.

This trial is in its early stages, with the main goal of finding the safest and most effective dose levels. Since these drugs are already approved for other uses, there is some reassurance about their safety in humans. However, discussing any concerns with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the triple therapy for small cell lung cancer because it combines atezolizumab, an immunotherapy, with niraparib and temozolomide, which have different mechanisms of action. While most treatments for small cell lung cancer focus on chemotherapy alone, this approach adds a PARP inhibitor, niraparib, which interferes with cancer cell repair, and temozolomide, an oral chemotherapy that can cross the blood-brain barrier. This combination aims to enhance the cancer-fighting effects by attacking the cancer cells on multiple fronts, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

This trial will compare two treatment approaches for extensive-stage small cell lung cancer. One group of participants will receive a combination of three drugs: temozolomide, niraparib, and atezolizumab. Studies have shown that this combination can be effective, with patients experiencing a median progression-free survival of 4.9 months. On average, their cancer did not worsen for about 4.9 months. Another group in this trial will receive only atezolizumab. Previous research indicates that this results in a median progression-free survival of 1.8 months. This suggests that the three-drug therapy could help control the cancer's growth for a longer time. The combination uses chemotherapy, targeted therapy, and immunotherapy to attack the cancer in different ways, potentially increasing its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Jonathan W. Goldman

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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, 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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03830918

Niraparib, Temozolomide and Atezolizumab in Treating ... Giving temozolomide, niraparib and atezolizumab may work better in treating patients with advanced solid tumors and extensive-stage small cell lung cancer.

2. cancernetwork.com cancernetwork.com/view/niraparib-triplet-shows-pfs-benefit-vs-atezolizumab-as-es-sclc-maintenance

Niraparib Triplet Shows PFS Benefit vs Atezolizumab as ... Efficacy data revealed that patients treated with the triplet therapy experienced a median PFS of 4.9 months vs 1.8 months with atezolizumab ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12437200/

State of the art in treatment of small cell lung cancer - PMC However, treatment resistance develops quickly, leading to poor overall survival and limited efficacy of subsequent therapies, especially for ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS9084

A phase Ib/II study of niraparib plus temozolomide ... This is a phase 1b/2, randomized, open-label study of TMZ plus niraparib, a PARP inhibitor, with atezolizumab versus atezolizumab as maintenance therapy in ...

5. spandidos-publications.com spandidos-publications.com/10.3892/ol.2025.15113

Six‑year survival after oral temozolomide maintenance ... The present study reported the case a patient with LS‐SCLC who received oral temozolomide (TMZ) maintenance therapy, achieving an impressive 6‐year survival.

6. aacrjournals.org aacrjournals.org/clincancerres/article/30/14/2872/746334/Facts-and-Hopes-on-Cancer-Immunotherapy-for-Small

Facts and Hopes on Cancer Immunotherapy for Small Cell ... Platinum-based chemotherapy plus PD1 axis blockade is the standard of care in the first-line treatment of extensive-stage small cell lung cancer (SCLC).