Pembrolizumab + Chemotherapy ± Canakinumab for Non-Small Cell Lung Cancer

(CANOPY-1 Trial)

Not currently recruiting at 180 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Immunotherapy, IL-1β inhibitors

Disqualifiers: EGFR mutations, ALK rearrangement, CNS metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 42

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for previously untreated non-small cell lung cancer (NSCLC). It tests pembrolizumab (an immunotherapy) with chemotherapy, with or without canakinumab (an anti-inflammatory drug that may reduce inflammation). The goal is to determine if these combinations can improve outcomes for patients with advanced NSCLC. Individuals with locally advanced or metastatic NSCLC who have not received prior treatments might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that using canakinumab and pembrolizumab together is generally safe for people with non-small cell lung cancer. Studies found that this combination can significantly slow the worsening of symptoms like chest pain and coughing. Researchers focused on safety, testing the treatment with standard chemotherapy drugs such as cisplatin and paclitaxel.

Cisplatin and paclitaxel are common chemotherapy drugs with well-known safety records, used for many years to treat various cancers. Pembrolizumab is also widely used for different types of cancer and is generally well-tolerated by patients.

While some side effects can occur, as with any cancer treatment, evidence suggests that this combination does not cause unexpected safety issues. Participants in past studies managed the side effects, and the treatment did not lead to any new, severe safety problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Pembrolizumab combined with chemotherapy is unique because it adds canakinumab, an anti-inflammatory drug, to the mix. This combination aims to enhance the immune system's ability to fight non-small cell lung cancer by using pembrolizumab, an immune checkpoint inhibitor, alongside platinum-based chemotherapies like cisplatin or carboplatin with paclitaxel. Researchers are excited because canakinumab could potentially reduce inflammation, which might improve treatment outcomes and offer a new mechanism of action compared to the standard chemotherapy and immunotherapy regimens. By targeting inflammation, this approach could offer an advantage over existing treatments by potentially improving patient responses and reducing side effects.

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

This trial will evaluate the combination of canakinumab with pembrolizumab and chemotherapy for non-small cell lung cancer (NSCLC). Studies have shown that adding canakinumab to pembrolizumab and chemotherapy did not significantly improve outcomes for people with NSCLC. Previous research found that this combination did not help patients live longer or slow the disease's progression. Pembrolizumab, however, is a well-known treatment that effectively treats certain types of lung cancer by helping the immune system fight cancer cells. Although the combination with canakinumab was safe, it did not enhance the effectiveness of pembrolizumab and chemotherapy alone. ^{2 3 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with advanced stage IIIB or IV non-squamous and squamous NSCLC who haven't had treatment before. They should have a performance status of 0 or 1, meaning they're fully active or restricted in physically strenuous activity but can do light work. No prior immunotherapy, drugs like canakinumab, certain genetic mutations (EGFR/ALK), compromised immune systems, recent vaccinations/surgeries/radiotherapy, or untreated brain metastases.

Inclusion Criteria

You have at least one specific type of visible abnormality that can be measured according to certain guidelines.

My PD-L1 status is known from a biopsy tested by a specific lab.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have previously been treated with canakinumab or similar drugs.

My cancer has specific changes in the EGFR gene or ALK rearrangement.

I have brain metastases or lepto-meningeal disease that hasn't been treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Safety and tolerability of pembrolizumab plus platinum-based doublet chemotherapy with canakinumab are assessed

6 weeks

During the first 42 days of dosing

Treatment

Participants receive pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 32 months

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab
• Cisplatin
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests the safety and effectiveness of pembrolizumab combined with platinum-based chemotherapy plus canakinumab versus placebo. It's a phase III trial where participants are randomly assigned to receive either the drug combo with canakinumab or without it (placebo) to compare outcomes.

How Is the Trial Designed?

Group I: Part 2: Placebo+pembro+CTx Experimental Treatment 7 Interventions

Double-blind, randomized, placebo-controlled, canakinumab-matching placebo in combination with pembrolizumab and platinum-based doublet chemotherapy.

Group II: Part 2: Canakinumab+pembro+CTx Experimental Treatment 7 Interventions

Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.

Group III: Part 1: Cohort C Experimental Treatment 4 Interventions

Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and paclitaxel.

Group IV: Part 1: Cohort B Experimental Treatment 4 Interventions

Safety run-in, canakinumab in combination with pembrolizumab, cisplatin, and pemetrexed.

Group V: Part 1: Cohort A Experimental Treatment 4 Interventions

Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and pemetrexed.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

This study is the first to evaluate the combination of necitumumab with pembrolizumab and platinum-based chemotherapy in patients with untreated squamous cell lung cancer (SqCLC), aiming to enhance tumor immunity and therapeutic effects.

The trial will assess safety and efficacy, with 42 patients enrolled in phase II to determine the overall response rate and other important outcomes like progression-free survival and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer Study: (NEJ048A/NEXUS). Miyanaga, A., Asahina, H., Watanabe, S., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a randomized phase 2 trial involving 101 patients with stage IV lung adenocarcinoma, the combination of Pemetrexed and Cisplatin (Pem-Cis) showed a significantly higher one-year survival rate of 72.0% compared to 52.9% for Docetaxel and Cisplatin (Doc-Cis).

Patients receiving Pem-Cis also experienced longer progression-free survival (12.6 months) compared to those on Doc-Cis (7.5 months), indicating that Pem-Cis may be a more effective first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. Su, SF., Li, M., Geng, YC., et al.[2020]

In a study of 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

In a multicenter study involving 130 patients with advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel and carboplatin resulted in a moderate response rate of 23.8%, indicating its efficacy as a treatment option.

Both high-dose (200 mg/m2) and low-dose (175 mg/m2) paclitaxel regimens were well tolerated, with myelosuppression being the most significant side effect, but differences in toxicity between the two doses were minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC). Glorieux, P., Ortmanns, P., Marien, S., et al.[2015]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

Recent advancements in pharmacogenomics have led to the development of novel agents for treating non-small cell lung cancer adenocarcinoma, emphasizing the importance of testing for specific mutations like EGFR and ALK in clinical practice.

Immunotherapy, particularly with agents like nivolumab and pembrolizumab, has emerged as a promising treatment for advanced non-small cell lung cancer, although monitoring for adverse effects is crucial during patient follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible adverse effects of immunotherapy in non-small cell lung cancer; treatment and follow-up of three cases. Zarogoulidis, P., Chinelis, P., Athanasiadou, A., et al.[2020]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

In the KEYNOTE-189 study, first-line treatment with pembrolizumab combined with pemetrexed-platinum significantly improved overall survival (OS) to a median of 22.0 months compared to 10.7 months for the placebo group, indicating a strong efficacy in treating metastatic nonsquamous non-small-cell lung cancer (NSCLC).

The combination therapy also resulted in a median progression-free survival (PFS) of 9.0 months versus 4.9 months for placebo, with benefits observed regardless of tumor PD-L1 expression or the presence of liver/brain metastases, while maintaining a similar incidence of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. Gadgeel, S., Rodríguez-Abreu, D., Speranza, G., et al.[2021]

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03631199

NCT03631199 | Study of Efficacy and Safety ... The study primarily assessed the safety and tolerability (safety run-in Part A) of pembrolizumab plus platinum-based doublet chemotherapy with canakinumab, ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.23.00980

Results From the CANOPY-1 Trial The addition of canakinumab to first-line pembrolizumab and CT did not prolong PFS or OS in patients with NSCLC.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12343357/

A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or ... No unexpected safety signals were observed and canakinumab did not adversely affect surgical outcomes. Intraoperative perihilar or perilobular fibrosis after ...

4. novartis.com novartis.com/news/media-releases/novartis-provides-update-phase-iii-study-evaluating-canakinumab-acz885-second-or-third-line-treatment-combination-chemotherapy-non-small-cell-lung-cancer

Novartis provides update on Phase III study evaluating ... Phase III CANOPY-2 trial did not meet primary endpoint of overall survival in patients with advanced or metastatic non-small cell lung ...

5. targetedonc.com targetedonc.com/view/canakinumab-with-pembrolizumab-shows-no-significant-survival-benefit-for-locally-advanced-or-metastatic-nsclc

Canakinumab With Pembrolizumab Shows No Significant ... The investigational combination of canakinumab plus pembrolizumab (Keytruda) did not achieve a statistically significant improvement in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38039427/

Results From the CANOPY-1 Trial Patients treated with canakinumab had clinically meaningful delays in deterioration of lung cancer symptoms, including chest pain and coughing ...

7. jtocrr.org jtocrr.org/article/S2666-3643(25)00076-1/fulltext

CANOPY-N: A Phase 2 Study of Canakinumab or ... CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canakinumab (200 mg subcutaneous once every three weeks) and ...

8. novctrd.com novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1547

Clinical Trial Results Summary A clinical trial to learn about the effects of canakinumab and pembrolizumab given alone or together before surgery to people with non-small cell lung cancer.