Immunotherapy + Chemotherapy for Non-Small Cell Lung Cancer

Overseen By Tina Cascone

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Hepatitis, HIV, 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: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining immunotherapy and chemotherapy for treating previously untreated non-small cell lung cancer. Researchers are testing nivolumab, an immunotherapy drug, both alone and with other treatments like ipilimumab (another immunotherapy drug) or chemotherapy drugs, to determine if they can more effectively target cancer cells. The trial includes individuals diagnosed with stage I to IIIA non-small cell lung cancer who have not received prior treatment. The study aims to determine if the combined treatments outperform chemotherapy alone. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study drugs. It's best to discuss your specific medications with the trial team.

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

A previous study found that nivolumab, a type of immunotherapy, had some serious side effects. The most common serious issues involved breathing, such as pneumonia and other respiratory problems. However, the FDA has already approved nivolumab for treating certain types of non-small cell lung cancer (NSCLC), indicating that its safety is fairly well understood for this cancer.

Research has shown that combining nivolumab with ipilimumab, another immunotherapy, can slightly increase side effects, but these are usually manageable. This combination has been safe enough for use in other NSCLC treatments and has demonstrated long-term benefits.

The chemotherapy drugs used in this trial—cisplatin, carboplatin, docetaxel, and pemetrexed—are also well-known. They can cause side effects like nausea or low blood cell counts, but these are typical and expected with chemotherapy.

In conclusion, previous studies suggest that the treatments in this trial have known safety profiles. While side effects are possible, they generally resemble those seen in other cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they integrate immunotherapy with chemotherapy, offering a potentially more effective approach. Nivolumab and ipilimumab are immunotherapy drugs that harness the body's immune system to target and destroy cancer cells, which is different from traditional chemotherapy that directly attacks the cancer. The combination of these immunotherapies with chemotherapy, like cisplatin or carboplatin, could enhance the body's natural defenses while also attacking the cancer cells directly. This dual approach might improve patient outcomes compared to standard treatments that rely solely on chemotherapy.

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

Research has shown that nivolumab, one of the treatments in this trial, holds promise for treating non-small cell lung cancer (NSCLC) when used alone or with other treatments. Participants may receive nivolumab alone or in combination with ipilimumab, which has increased survival rates for NSCLC patients. Studies indicate that nivolumab can more than double the average survival time compared to standard treatments. When combined with ipilimumab, patients tend to live longer and respond better than with chemotherapy alone. In this trial, some participants will receive a combination of nivolumab, ipilimumab, and chemotherapy, which can further improve survival chances. These treatments help the immune system identify and attack cancer cells, slowing the growth and spread of tumors. ^{6 7 8 9 10}

Who Is on the Research Team?

Tina Cascone

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with untreated stage I-IIIA non-small cell lung cancer who are suitable for surgery, have good organ function and performance status (able to carry out daily activities), and can provide consent. They must not be pregnant, on current cancer therapy, or have severe allergies to monoclonal antibodies or certain chemotherapy drugs.

Inclusion Criteria

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

My lung cancer diagnosis was confirmed through lab tests and has not been treated yet.

My cancer is at stage IB (>=4 cm), IIA, IIB, or IIIA.

Exclusion Criteria

I am currently undergoing cancer treatment or participating in a drug trial.

I have hearing loss as confirmed by an audiologist.

Unwillingness or inability to follow the procedures required in the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive nivolumab alone or in combination with ipilimumab or chemotherapy

6 weeks

3 visits (in-person)

Surgery

Surgical resection of the tumor is performed

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Docetaxel
• Ipilimumab
• Nivolumab
• Pemetrexed

Trial Overview The study tests how well nivolumab works alone or combined with ipilimumab or chemotherapy (cisplatin, docetaxel, pemetrexed) in treating these lung cancer patients. It compares the effectiveness of immunotherapy versus traditional chemotherapy in stopping tumor growth.

How Is the Trial Designed?

Group I: Arm D (ipilimumab, nivolumab, chemotherapy) Experimental Treatment 6 Interventions

Patients receive ipilimumab IV over 90 minutes on day 1, nivolumab IV over 30 minutes on days 1, 22, and 43, and cisplatin (or carboplatin) IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

Group II: Arm C (nivolumab, cisplatin, docetaxel, pemetrexed) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 30 minutes and cisplatin IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

Group III: Arm B (nivolumab, ipilimumab) Experimental Treatment 2 Interventions

Participants receive nivolumab as in Arm A and receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity.

Group IV: Arm A (nivolumab) Experimental Treatment 1 Intervention

Participants receive nivolumab IV over 60 minutes on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. opdivo.com opdivo.com/nsclc/clinical-trial-results/advanced-previously-treated-immunotherapy

Clinical trial results for previously treated stage 4 recurrent ... 42% of patients given OPDIVO® (nivolumab) for advanced squamous NSCLC were alive. People ...

2. opdivohcp.com opdivohcp.com/efficacy/nsclc

Efficacy Data for Non-Small Cell Lung Cancer (NSCLC) - Opdivo Fatal adverse reactions occurred in 3.6% of patients who received OPDIVO in combination with chemotherapy; these included sepsis (1%). OPDIVO and/or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4346216/

Nivolumab in NSCLC: latest evidence and clinical potential This review will discuss results from early phase studies of nivolumab in solid tumors including non-small cell lung cancer (NSCLC)

4. sciencedirect.com sciencedirect.com/science/article/pii/S152573042030231X

Real-World Effectiveness of Nivolumab Monotherapy After ... This study confirmed the effectiveness of nivolumab monotherapy for previously treated advanced NSCLC in real-world clinical practice.

5. jto.org jto.org/article/S1556-0864(24)02355-4/fulltext

Long-Term Survival Outcomes With First-Line Nivolumab ... In patients with squamous NSCLC, median OS was 16.2 versus 8.2 months with nivolumab plus ipilimumab with or without chemotherapy versus ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12206876/

Real-world safety of carboplatin in non-small cell lung cancer This study aims to systematically assess carboplatin-related AEs and explore demographic factors that may influence risk.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225000966

Efficacy and safety of first-line pemetrexed plus carboplatin ... Efficacy and safety of first-line pemetrexed plus carboplatin followed by pemetrexed maintenance in newly diagnosed and metastatic elderly non-squamous ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3290110/

Safety and Efficacy of Pemetrexed in Maintenance Therapy of ... Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer.

9. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2762583

Comparison of Carboplatin Plus Pemetrexed Followed by ... This phase 3 randomized clinical trial compares treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance with docetaxel ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT00520676

Chemotherapy in Treating Patients With Non-Small Cell ... The purpose of this study is to compare the combination of pemetrexed and carboplatin with the combination of docetaxel and carboplatin in terms of survival ...