Camu Camu + ICI for Non-Small Cell Lung Cancer

Recruiting at 2 trial locations

Overseen By Wiam Belkaid, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must be taking: Anti-PD-1, Platinum-doublet

Must not be taking: Probiotics, Prebiotics, Antibiotics

Disqualifiers: Pregnancy, Severe immunodeficiency, CNS metastases, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 3 months

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a natural berry supplement to improve gut health in patients with advanced lung cancer and melanoma. These patients often do not respond well to current treatments. The supplement works by increasing beneficial gut bacteria, potentially making cancer treatments more effective. Berries have shown potential against several cancers, including lung cancer and melanoma, by influencing cellular processes and improving gut health.

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

The trial requires you to stop taking probiotics and prebiotics at least 2 weeks before starting, and you cannot take them during the trial. Antibiotics should also be stopped 2 weeks before, but if needed during the trial, you can continue. Other medications are not specifically mentioned, so check with the trial team.

What data supports the effectiveness of the drug Camu Camu + ICI for Non-Small Cell Lung Cancer?

Research shows that combining nivolumab and ipilimumab, which are part of the immune checkpoint inhibitors (drugs that help the immune system fight cancer), can improve survival in patients with advanced non-small cell lung cancer compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of Camu Camu and immune checkpoint inhibitors safe for humans?

Immune checkpoint inhibitors like nivolumab and ipilimumab can cause serious side effects, including heart problems and immune-related reactions affecting the skin, liver, and lungs. While these side effects are rare, they should be monitored closely. There is no specific safety data available for Camu Camu in combination with these drugs. ^{6 7 8 9 10}

How is the Camu Camu + ICI treatment different from other drugs for non-small cell lung cancer?

The Camu Camu + ICI treatment is unique because it combines natural ingredients from Camu Camu with immune checkpoint inhibitors (drugs that help the immune system attack cancer cells), which may offer a novel approach compared to traditional chemotherapy or ICI alone. ^{4 11 12 13 14}

Research Team

Arielle Elkrief, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) or melanoma, who are receiving standard immune checkpoint inhibitors (ICIs). Participants must not have had prior anti-PD1 treatments (except specific melanoma patients), be able to swallow capsules, and use effective contraception. Exclusions include recent probiotic/prebiotic use, severe immunodeficiency, active infections requiring systemic therapy, certain autoimmune diseases, and pregnancy.

Inclusion Criteria

I have not received anti-PD1 treatment before, unless I am in cohort 3.

I have been treated with BRAF-targeting drugs before.

I can take care of myself and perform daily activities.

Exclusion Criteria

I am taking medication for an autoimmune disease that is not under control.

I am currently being treated for an infection.

I have only received the flu shot and COVID-19 vaccines, not the nasal spray flu vaccine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Camu Camu prebiotic in combination with standard-of-care immune checkpoint inhibitors

3 months

Every 21 or 28 days, depending on ICI treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

Treatment Details

Interventions

• Camu Camu Capsules
• Immune Checkpoint Inhibitors

Trial Overview The study tests the safety and tolerability of Camu Camu (CC) prebiotic capsules in combination with standard ICIs in treating NSCLC and melanoma. CC may enrich beneficial gut bacteria linked to better ICI response. Patients are grouped based on their disease stage and treatment regimen.

Participant Groups

Group I: Camu-camu (intervention) in addition to standard-of-care ICI Experimental Treatment 1 Intervention

Camu-camu (intervention) will be added to standard-of-care ICI in: Cohort 1. For patients with advanced NSCLC, treatment will consist of single-agent pembrolizumab in combination with physician's choice platinum-doublet chemotherapy in combination with CC. Cohort 2. For patients with advanced cutaneous melanoma, treatment will consist of single-agent anti-PD-1 either nivolumab or pembrolizumab at the discretion of the treating physician. Cohort 3. For patients with advanced melanoma receiving standard-of-care ICI (either single-agent anti-PD-1 or combination anti-CTLA-4 plus anti-PD-1) who experience progressive disease (PD), their current regimen will continue unchanged and they will receive CC at 1500 mg for 3 months or until confirmed progression if progression occurs earlier.

Immune Checkpoint Inhibitors is already approved in European Union, United States for the following indications:

Approved in European Union as Nivolumab for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Squamous cell carcinoma of the head and neck

Approved in United States as Nivolumab for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Squamous cell carcinoma of the head and neck

Approved in European Union as Ipilimumab for:

• Melanoma

Approved in United States as Ipilimumab for:

• Melanoma

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Findings from Research

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]

Combining immune checkpoint inhibitors (ICIs) with conventional treatments significantly improves progression-free survival (PFS) and overall survival (OS) in advanced lung cancer patients, with a pooled analysis of 13 trials involving 9,241 participants showing a PFS hazard ratio of 0.66 and an OS hazard ratio of 0.77.

The greatest improvements in PFS and OS were observed with PD-1-based combinations, while the effectiveness of the treatment varied based on PD-L1 expression levels, particularly benefiting males, current or former smokers, non-squamous patients, and those without driver mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of clinicopathological features on the efficacy of immune checkpoint inhibitors plus conventional treatment in patients with advanced lung cancer. Gao, G., Qiao, M., Liu, H., 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]

Immune checkpoint inhibitor (ICI) therapy in lung cancer shows a significant survival benefit, with pooled overall survival Cox hazard ratios indicating improved outcomes for patients with higher PD-L1 expression levels, particularly those with PD-L1 ≥ 50% (HR 0.62).

Approximately 10% of patients treated with ICI achieved long-term survival across different treatment lines, although for patients with PD-L1 < 1%, the long-term survival and short-term survival rates did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit. Lin, EP., Hsu, CY., Chiou, JF., 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 a study of 373 patients from 11 phase I clinical trials, ipilimumab-related grade 3/4 adverse events were more common in patients who responded to treatment, indicating a potential link between therapeutic response and toxicity.

The likelihood of experiencing severe adverse events increased with the number of additional agents used alongside ipilimumab, while longer treatment duration was associated with more low-grade toxicities but not high-grade ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials. Chauhan, A., Kabir, T., Wu, J., et al.[2023]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

Immunotherapy targeting PD-1/PD-L1 and CTLA-4 has shown increased survival benefits in treating metastatic non-small cell lung cancer (NSCLC), but it is also associated with significant cardiotoxicity, particularly high-grade conduction disorders like 3rd degree heart block.

A case study highlighted a patient who developed 3rd degree heart block 16 days after starting combination therapy with ipilimumab and nivolumab, emphasizing that over 75% of immunotherapy-related cardiotoxicity cases occur within the first 6 weeks, which underscores the need for early identification and monitoring of high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy-associated complete heart block in a patient with NSCLC: A case report and literature review. Vartanov, A., Kalotra, A., Varughese, J., et al.[2021]

A meta-analysis of 21 trials involving 11,454 patients found that immune checkpoint inhibitors (ICIs) significantly increase the risk of various immune-related adverse events (irAEs), including colitis, liver enzyme elevation, rash, hypothyroidism, and pneumonitis compared to non-ICI treatments.

While the incidence of fatal irAEs was less than 1%, the study highlights the importance of early recognition and intervention for these adverse events to prevent complications, particularly noting that ipilimumab was linked to a higher risk of certain skin and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients. De Velasco, G., Je, Y., Bossé, D., et al.[2023]

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]

Combining immune checkpoint inhibitors (ICI) with chemotherapy (CT) significantly improves overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) in patients with advanced non-small-cell lung cancer (NSCLC), based on a review of 8 randomized controlled trials involving 4227 patients.

However, this combination treatment is associated with a higher incidence of severe treatment-related adverse events (grade 3-5), indicating a trade-off between improved efficacy and increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of immune checkpoint inhibitor plus chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis. Meng, LF., Huang, JF., Luo, PH., et al.[2022]

In a study of 139 non-small-cell lung cancer (NSCLC) patients treated with nivolumab, high levels of CD8+ and CD4+ immune cell infiltration in the tumor stroma were associated with significantly better overall survival (9.0 months) compared to lower levels (5.0 months).

Biopsies taken after the last line of chemotherapy were more predictive of durable clinical benefit and overall survival than those taken before chemotherapy, indicating that chemotherapy may alter the immune microenvironment and affect treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of tumour and stroma PD-1, PD-L1, CD3, CD4 and CD8 expression with DCB and OS to nivolumab treatment in NSCLC patients pre-treated with chemotherapy. Niemeijer, AN., Sahba, S., Smit, EF., et al.[2021]

In a study of 128 patients with previously treated non-small cell lung cancer (NSCLC), the combination of nivolumab and docetaxel significantly improved overall survival (OS) to 23.1 months compared to 14.7 months with nivolumab alone.

The combination therapy also resulted in a longer progression-free survival (PFS) of 6.7 months versus 3.1 months for nivolumab alone, although it was associated with higher rates of hematotoxicity and gastrointestinal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non-Small Cell Lung Cancer: TORG1630. Taniguchi, Y., Shimokawa, T., Takiguchi, Y., et al.[2023]

Combining immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 with chemotherapy significantly improves overall survival and progression-free survival in small cell lung cancer patients, with hazard ratios of 0.83 and 0.80, respectively, based on a review of five studies.

The combination treatment does not increase the rate of severe adverse events compared to conventional chemotherapy, indicating that it is a tolerable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer. Wu, J., Zhang, A., Li, L., et al.[2021]

References

1. 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]

2. China pubmed.ncbi.nlm.nih.gov

Impact of clinicopathological features on the efficacy of immune checkpoint inhibitors plus conventional treatment in patients with advanced lung cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit. [2023]

5. 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]

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

Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Immunotherapy-associated complete heart block in a patient with NSCLC: A case report and literature review. [2021]

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

Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients. [2023]

10. Spain pubmed.ncbi.nlm.nih.gov

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

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

The efficacy and safety of immune checkpoint inhibitor plus chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Association of tumour and stroma PD-1, PD-L1, CD3, CD4 and CD8 expression with DCB and OS to nivolumab treatment in NSCLC patients pre-treated with chemotherapy. [2021]

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

A Randomized Comparison of Nivolumab versus Nivolumab + Docetaxel for Previously Treated Advanced or Recurrent ICI-Naïve Non-Small Cell Lung Cancer: TORG1630. [2023]

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

Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer. [2021]