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

Must be taking: Anti-PD1, PDL1 antibodies

Must not be taking: Antibiotics, Anti-cancer therapy

Disqualifiers: Pregnancy, Autoimmune disease, Pneumonitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for advanced non-small cell lung cancer (NSCLC) that has worsened after certain treatments. It combines two immunotherapy drugs, Nivolumab (Opdivo) and Ipilumumab, with a low dose of the chemotherapy drug Oxaliplatin (Eloxatin) to evaluate effectiveness and safety. The trial targets individuals whose lung cancer has advanced despite previous treatments, including specific immunotherapies and chemotherapy. Participants must have been diagnosed with advanced NSCLC and experienced disease progression after using immune-targeting drugs. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's effects and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in cancer therapy.

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.

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

Research has shown that the combination of Nivolumab, Oxaliplatin, and Ipilimumab has been studied for safety in treating non-small cell lung cancer (NSCLC). Nivolumab and Ipilimumab, types of immunotherapy, help the body's immune system fight cancer. They have been used together for certain cancers, including NSCLC, and studies have found that patients generally tolerate this combination well. However, some people may experience side effects like tiredness, skin rash, and diarrhea.

Oxaliplatin, a chemotherapy drug, can enhance the effects of immunotherapy by helping the immune system attack cancer cells. While effective, it might also cause side effects such as nausea and nerve damage, leading to tingling or numbness, especially in the hands and feet.

Overall, these treatments are generally considered safe, but they do have potential risks. Prospective trial participants should discuss these risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ipilimumab, Nivolumab, and Oxaliplatin for non-small cell lung cancer because it offers a novel approach by harnessing the power of immunotherapy alongside chemotherapy. Unlike traditional chemotherapy alone, this treatment engages the immune system, with Ipilimumab and Nivolumab targeting specific proteins that often help cancer cells evade detection, potentially leading to a more robust anti-cancer response. Oxaliplatin, a platinum-based drug, adds a chemotherapy component that can directly kill cancer cells. This multi-pronged strategy could improve outcomes by not only attacking cancer cells directly but also by strengthening the body's natural defenses against the tumor.

What evidence suggests that this trial's treatments could be effective for advanced NSCLC?

This trial will evaluate the combination of Nivolumab, Ipilimumab, and Oxaliplatin for patients with advanced non-small cell lung cancer (NSCLC). Studies have shown that using Nivolumab and Ipilimumab together can nearly double survival rates compared to chemotherapy alone. When combined with chemotherapy, Nivolumab has helped patients live longer without cancer progression. Adding Oxaliplatin, another chemotherapy drug, aims to enhance this effect further. Previous research demonstrated that patients treated with these combinations experienced better survival rates and improved disease control. These findings suggest that using these treatments together could be effective for those whose cancer did not respond to earlier immunotherapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Hatim Husain

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. opdivohcp.com opdivohcp.com/efficacy/nsclc

Efficacy Data for Non-Small Cell Lung Cancer (NSCLC) - Opdivo Find OPDIVO® (nivolumab) efficacy information for the treatment of non-small cell lung cancers. Please see Indications and Important Safety Information.

2. opdivo.com opdivo.com/nsclc/clinical-trial-results/advanced-immunotherapy-combination-chemo

Stage 4 Advanced PD-L1 Positive Non-Small Cell Lung ... In an analysis with a minimum follow-up of 7 months, half of the people given OPDIVO + YERVOY and platinum-based chemotherapy lived 7 months without their ...

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. news.bms.com news.bms.com/news/details/2022/Landmark-Five-Year-Data-from-Phase-3-CheckMate--227-Trial-Demonstrate-Long-Term-Durable-Survival-Outcomes-with-Opdivonivolumab-Plus-Yervoy-ipilimumab-in-First-Line-Treatment-of-Patients-with-Metastatic-Non-Small-Cell-Lung-Cancer/default.aspx

Landmark Five-Year Data from Phase 3 CheckMate -227 ... Opdivo plus Yervoy nearly doubled overall survival rate at five years compared to chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC)

5. opdivohcp.com opdivohcp.com/efficacy/nsclc/opdivo

5 years of OS data in 2L mNSCLC 1,2 - Opdivo Long-term survival outcomes with nivolumab in patients with previously treated advanced non-small cell lung cancer: impact of early disease control and response ...

6. opdivohcp.com opdivohcp.com/safety/nsclc

Safety Profile for Non-Small Cell Lung Cancer (NSCLC) View the OPDIVO® (nivolumab) safety profiles for the treatment of metastatic non-small cell lung cancers (mNSCLC). Please see Indications and Important ...

7. opdivo.com opdivo.com/nsclc

Non-Small Cell Lung Cancer (NSCLC) Treatment OPDIVO® (nivolumab) alone, or with YERVOY® (ipilimumab) can be used as an immunotherapy treatment option for adults with certain types of NSCLC.

8. packageinserts.bms.com packageinserts.bms.com/pi/pi_opdivo.pdf

OPDIVO U.S. Prescribing Information The safety of OPDIVO with ipilimumab was evaluated in CHECKMATE-214, a randomized ... • adults with a type of lung cancer called non-small cell lung cancer (NSCLC) ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6386029/

Safety and efficacy of nivolumab in combination with S-1 ... It is reported that oxaliplatin can induce immunologic death of cancer cells and thereby enhance the efficacy of immuno-oncology agents. This phenomenon, ...

10. mayoclinic.org mayoclinic.org/drugs-supplements/nivolumab-intravenous-route/description/drg-20127723

Nivolumab (intravenous route) - Side effects & uses Nivolumab injection is also used to treat non-small cell lung cancer (NSCLC) ... Safety and efficacy have not been established in children ...