Immunotherapy + Chemotherapy for Non-Small Cell Lung Cancer

(NSCLC Trial)

Overseen By Hatim Husain

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hatim Husain

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any approved anti-cancer therapy at least 2 weeks before starting the study treatment. If you are on any investigational drugs or antibiotics, you must stop them 21 days and 2 weeks before enrollment, respectively.

What data supports the effectiveness of the drug combination of Ipilimumab, Nivolumab, Opdivo, Oxaliplatin, and Eloxatin for treating non-small cell lung cancer?

Research shows that using nivolumab (Opdivo) and ipilimumab together can help people with advanced non-small cell lung cancer live longer compared to just using chemotherapy. This combination has shown durable and long-term effectiveness in patients with this type of lung cancer. ^{1 2 3 4 5}

Is the combination of immunotherapy drugs nivolumab and ipilimumab safe for humans?

The combination of nivolumab and ipilimumab has been studied in patients with non-small cell lung cancer and melanoma, showing a manageable safety profile, though it can lead to immune-related side effects. These side effects are specific to each drug and can combine when used together, but they are generally considered manageable with proper guidelines. ^{3 5 6 7 8}

How is the drug combination of Ipilimumab, Nivolumab, and Oxaliplatin unique for treating non-small cell lung cancer?

This drug combination is unique because it combines two immune checkpoint inhibitors, Ipilimumab and Nivolumab, which work by boosting the body's immune response against cancer cells, with Oxaliplatin, a chemotherapy drug. This approach aims to enhance the effectiveness of treatment by using both immunotherapy and chemotherapy, potentially improving survival rates in patients with advanced non-small cell lung cancer. ^{2 9 10 11 12}

What is the purpose of this trial?

The purpose of this study is to examine the safety and efficacy of combining Nivolumab and low-dose Oxaliplatin with or without Ipilumumab in patients who have had their advanced NSCLC cancer worsen on or after being treated with certain immunotherapies (drugs that target the immune system).

Research Team

Hatim Husain

Principal Investigator

University of California, San Diego

Eligibility Criteria

Adults with advanced non-small cell lung cancer (NSCLC) that worsened after immunotherapy can join. They must have measurable disease, agree to use effective contraception, and not exceed three prior therapies including one with anti-PD1 or PDL1 antibodies. Excluded are those with severe allergies to certain proteins, autoimmune diseases, recent major surgeries, organ transplants, antibiotic use within two weeks before the trial or women who are pregnant.

Inclusion Criteria

My recent blood and organ function tests are within normal ranges.

I am not postmenopausal or surgically sterile and have a recent negative pregnancy test.

My last treatment for advanced lung cancer was with an anti-PD1 or PDL1 drug, and I've had no more than 3 treatments.

Exclusion Criteria

I haven't had cancer treatment in the last 2 weeks.

I have had a bone marrow or organ transplant.

I have taken antibiotics by mouth or IV in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab, Oxaliplatin, and Ipilimumab to assess safety and efficacy

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Ipilumumab
• Nivolumab
• Oxaliplatin

Trial Overview The study tests Nivolumab combined with low-dose Oxaliplatin and possibly Ipilimumab in NSCLC patients post-immunotherapy failure. Nivolumab targets PD-1 on immune cells; Ipilimumab binds CTLA-4 protein; Oxaliplatin is an immunogenic chemotherapy aiming to boost the body's immune response against cancer.

Participant Groups

Group I: Nivolumab + Oxaliplatin + Ipilimumab Experimental Treatment 3 Interventions

Cohort 1

Who Is Running the Clinical Trial?

Hatim Husain

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

In a study of 184 patients with non-small cell lung cancer treated with immune checkpoint inhibitors, 26.6% developed immune-related adverse events (IRAEs), with certain factors like statin use and previous corticosteroid therapy increasing the risk of IRAEs.

Interestingly, patients who experienced IRAEs had significantly better progression-free survival (41 weeks vs. 9 weeks) and overall survival (89 weeks vs. 28 weeks), suggesting that the occurrence of IRAEs may be linked to improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. Serino, M., Freitas, C., Martins, M., et al.[2022]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

In a phase I study involving 15 Japanese patients with advanced non-small-cell lung cancer (NSCLC), the recommended dose of ipilimumab in combination with paclitaxel and carboplatin was determined to be 10 mg/kg, showing a manageable safety profile.

The study found that the most common adverse events were related to blood cell counts and immune responses, with three patients in each dose cohort achieving a partial response, indicating potential efficacy of the treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer. Horinouchi, H., Yamamoto, N., Fujiwara, Y., et al.[2022]

The combination of nivolumab and ipilimumab has shown promise as a first-line treatment for previously untreated advanced non-small-cell lung cancer, as demonstrated in the Phase III CheckMate 227 study.

This study is significant because it is the first to evaluate a chemotherapy-sparing approach using dual immune checkpoint inhibition, while also considering tumor mutational burden as a biomarker for selecting suitable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in non-small-cell lung cancer. Reck, M., Borghaei, H., O'Byrne, KJ.[2019]

Ipilimumab, an anti-CTLA-4 antibody, can lead to a complete response in a stage IV adenocarcinoma patient when used as maintenance therapy after initial chemotherapy, demonstrating its potential efficacy in treating non-small cell lung cancer.

Despite causing significant gastrointestinal toxicity (grade 3), the patient maintained a complete response for 6 years, highlighting the need to further understand the balance between efficacy and side effects in immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ipilimumab and metastatic lung cancer: Can we change the natural history of the disease?]. Boyer, A., Greillier, L., Barazzutti, H., et al.[2017]

Immunotherapy is becoming a key part of first-line treatment for non-small cell lung cancer (NSCLC), with various phase 3 studies showing the effectiveness of drugs targeting PD-1, PD-L1, and CTLA-4, often in combination with chemotherapy.

Patients with high PD-L1 expression (≥ 50%) can be treated with single-agent Pembrolizumab or Atezolizumab, while those with lower expression have multiple treatment options, including combinations of immunotherapy and chemotherapy, highlighting the tailored approach based on tumor characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line Immunotherapy for Non-Small Cell Lung Cancer. Nasser, NJ., Gorenberg, M., Agbarya, A.[2020]

References

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

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021]

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

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]

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

Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

6. Spain pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. [2022]

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

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]

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

Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in non-small-cell lung cancer. [2019]

11. France pubmed.ncbi.nlm.nih.gov

[Ipilimumab and metastatic lung cancer: Can we change the natural history of the disease?]. [2017]

12. Switzerland pubmed.ncbi.nlm.nih.gov

First line Immunotherapy for Non-Small Cell Lung Cancer. [2020]