Chemotherapy + Immunotherapy for Lung Cancer

Recruiting at 10 trial locations

Overseen By Missak Haigentz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rutgers, The State University of New Jersey

Must not be taking: Checkpoint inhibitors, Immunosuppressants

Disqualifiers: Small cell carcinoma, Autoimmune conditions, 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: 3

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment schedule for individuals with advanced lung or head and neck cancers. It combines chemotherapy and immunotherapy, using drugs like pembrolizumab, to evaluate the effectiveness of this combination against these cancers. Individuals diagnosed with advanced lung cancer or specific types of head and neck cancer, who have not received prior treatment for metastatic disease, might be suitable candidates for this study. The trial organizes participants into groups based on cancer type to tailor the treatment approach. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have received prior systemic chemotherapy or immunotherapy for advanced metastatic NSCLC or recurrent/metastatic head and neck cancer. Some low-dose chemotherapeutics for non-malignant conditions may be allowed with review, and you must not be on immunosuppressive medication within 7 days prior to randomization.

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

Research shows that the treatments tested in this trial have been studied before and are generally safe for patients.

For the combination of carboplatin, paclitaxel, and pembrolizumab, studies have shown that this mix is safe and extends patient survival compared to chemotherapy alone. Serious side effects occurred, but these were manageable and expected with cancer treatments.

The combination of carboplatin, pemetrexed, and pembrolizumab has also shown positive results in previous studies. Some patients experienced severe side effects, but these were typical for such treatments.

Lastly, the combination of carboplatin, 5-fluorouracil, and pembrolizumab has been used in head and neck cancer treatments. Studies found it effective, with a safety profile similar to other cancer drug combinations. Serious side effects were present but did not outweigh the benefits.

Overall, these treatments have been well-studied and are considered safe, with side effects typical for cancer therapies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine chemotherapy and immunotherapy in a novel way to tackle lung cancer and head and neck squamous cell carcinoma. Unlike standard treatments, which often rely solely on chemotherapy, this approach uses pembrolizumab, an immunotherapy drug, alongside traditional chemotherapy agents like carboplatin and paclitaxel. Pembrolizumab works by enhancing the body's immune response to better target and destroy cancer cells. This combination aims to improve treatment effectiveness and potentially extend survival, offering hope for better outcomes than current standard care options.

What evidence suggests that this trial's treatments could be effective for lung and head and neck cancers?

Research has shown that combining chemotherapy with pembrolizumab may be promising for treating advanced lung and head and neck cancers. In this trial, participants with squamous lung cancer will receive either a combination of carboplatin, paclitaxel, and pembrolizumab or carboplatin, nab-paclitaxel, and pembrolizumab. Studies have found that adding pembrolizumab to chemotherapy helps patients live longer compared to using chemotherapy alone. For non-squamous lung cancer, participants will receive carboplatin, pemetrexed, and pembrolizumab, a combination that has proven very effective, with 86% of patients responding well to the treatment. Participants with head and neck squamous cell carcinoma will receive pembrolizumab with carboplatin and 5-fluorouracil, which has also been effective in extending patient survival compared to other treatments. These findings suggest that this treatment approach can be effective for these types of cancer, offering hope for better outcomes. ^{4 5 6 7 8}

Who Is on the Research Team?

Missak Haigentz, MD

Principal Investigator

Rutgers Cancer Institute of New Jersey

Are You a Good Fit for This Trial?

This trial is for adults with advanced lung or head and neck cancers. Participants must have a certain level of physical fitness (ECOG 0-2) and measurable disease. They should not be pregnant, breastfeeding, or have severe infections, organ transplants, autoimmune diseases requiring treatment in the past 2 years, known specific cancer mutations, or pre-existing severe lung conditions.

Inclusion Criteria

Patients may have ANY PD-L1 expression Tumor Proportion Score (TPS) status

My cancer is not small cell carcinoma.

My brain scans show no worsening after treatment for brain metastases.

Exclusion Criteria

My cancer does not have treatable mutations like EGFR (except exon 20), BRAF (V600), MET Exon14, ALK, or ROS1.

I have a history of cancer.

I haven't had any cancer except for skin cancer in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Alternating cycles of induction chemoimmunotherapy and immunotherapy alone

18-30 weeks

Visits every 3-6 weeks

Maintenance

Maintenance cycles with Pemetrexed and Pembrolizumab or Pembrolizumab alone

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• 5Fluorouracil
• Carboplatin
• Paclitaxel
• Pembrolizumab
• Pemetrexed

Trial Overview The study tests alternating cycles of chemoimmunotherapy (chemo drugs like Paclitaxel combined with Pembrolizumab) and immunotherapy alone as initial treatments. It aims to see if changing treatment types can better manage advanced cancers.

How Is the Trial Designed?

Group I: Squamous Lung Cancer Experimental Treatment 3 Interventions

A Cycles consist of either: * Paclitaxel Based: Carboplatin/Paclitaxel/Pembrolizumab OR * nab-Paclitaxel Based: Carboplatin/nab Paclitaxel/Pembrolizumab These A Cycles will be given for up to four cycles (standard) B Cycles consist of Pembrolizumab alone

Group II: Non-Squamous Lung Cancer Experimental Treatment 3 Interventions

* A Cycles consist of Carboplatin/Pemetrexed/Pembrolizumab (up to four cycles standard) * B Cycles consist of Pembrolizumab alone Maintenance Cycles (Cycle 5 and beyond): Pemetrexed in combination with Pembrolizumab; Alternatively, Pembrolizumab alone, for up to 2 years since enrollment (standard)

Group III: Head and Neck Squamous Cell Carcinoma Experimental Treatment 3 Interventions

* A Cycles consist of Carboplatin/5-Fluorouracil/Pembrolizumab (up to six cycles standard) * B Cycles consist of Pembrolizumab alone Maintenance Cycles (Cycle 7 and beyond): Pembrolizumab alone, for up to two years since enrollment (standard)

5Fluorouracil is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Efudex for:

• Actinic keratosis
• Basal cell carcinoma

Approved in Canada as Efudex for:

• Actinic keratosis
• Basal cell carcinoma

Approved in United States as Adrucil for:

• Anal Cancer
• Breast Cancer
• Cervical Cancer
• Colorectal Cancer
• Nasopharyngeal Carcinoma
• Pancreatic Cancer
• Stomach Cancer

Approved in European Union as Fluorouracil for:

• Actinic keratosis
• Basal cell carcinoma
• Anal Cancer
• Breast Cancer
• Cervical Cancer
• Colorectal Cancer
• Nasopharyngeal Carcinoma
• Pancreatic Cancer
• Stomach Cancer

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Published Research Related to This Trial

Pemetrexed (Alimta) shows a response rate of 16%-23% as a single agent for non-small-cell lung cancer (NSCLC) and a higher response rate of 38.9%-44.8% when combined with cisplatin, leading to a median survival of 8.9-10.9 months.

The main side effect of pemetrexed is neutropenia, but this can be mitigated with vitamin B12 and folate supplements, highlighting the importance of supportive care in enhancing treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed (Alimta): a new antifolate for non-small-cell lung cancer. Ettinger, DS.[2017]

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]

Pemetrexed is an effective treatment for advanced non-squamous non-small cell lung cancer (NSCLC), recommended by ASCO for first-line, maintenance, and subsequent treatments, and is generally well tolerated with minimal side effects.

Despite its overall safety profile, there is a risk of severe anaphylactic reactions, as demonstrated by a case of a patient with stage IV adenocarcinoma who required ventilatory support after receiving pemetrexed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed Induced Life-threatening Anaphylaxis. Rajasurya, V., Pyakuryal, B., Gunasekaran, K., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In the phase III KEYNOTE-189 study, pembrolizumab combined with pemetrexed and platinum-based chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with untreated metastatic nonsquamous non-small-cell lung cancer, with a hazard ratio of 0.56 for OS and 0.49 for PFS after a median follow-up of 31 months.

The treatment was associated with a high objective response rate (ORR) of 48.3% compared to 19.9% for the placebo group, and among patients who completed 35 cycles of pembrolizumab, the ORR was even higher at 85.7%, indicating strong efficacy with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Rodríguez-Abreu, D., Powell, SF., Hochmair, MJ., 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]

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Pemetrexed, when combined with carboplatin, has shown promising antitumor activity with mild toxicity in phase II clinical trials, but it can lead to serious adverse reactions such as toxic epidermal necrolysis, as seen in a reported case.

Supplementation with folic acid and vitamin B12 is recommended during pemetrexed treatment to help reduce the risk of hematological and gastrointestinal side effects, although severe skin reactions can still occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis related to pemetrexed and carboplatin with vitamin B12 and folic acid supplementation for advanced non-small cell lung cancer. Bosch-Barrera, J., Gaztañaga, M., Ceballos, J., et al.[2015]

In a systematic review and network meta-analysis of first-line treatments for metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC), the combination of pembrolizumab, pemetrexed, and platinum showed a statistically significant improvement in overall survival compared to various other regimens, with hazard ratios ranging from 0.42 to 0.62.

This combination therapy had a 95.6% probability of being the most effective treatment option for overall survival in patients without known targetable mutations, indicating its strong potential as a first-line treatment for this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. Frederickson, AM., Arndorfer, S., Zhang, I., et al.[2022]

Citations

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Cost-effectiveness of pembrolizumab for the first-line ... The study evaluates the cost-effectiveness of pembrolizumab in combination with platinum and 5-fluorouracil, against the Extreme regime in Colombia using both ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e18006

Comparative efficacy of pembrolizumab with carboplatin ... This NMA with MAIC suggests patients treated with the KNB10 regimen had improved or comparable ORR outcomes versus other recommended 1L interventions for R/M ...

3. keytrudahcp.com keytrudahcp.com/efficacy/hnscc-first-line-combination-therapy/

KEYNOTE-048 - Clinical Trial Results for First-line ... Health care professionals may find clinical trial results from KEYNOTE-048 in first-line combination therapy in patients with metastatic or unresectable, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804925001765

5-year follow-up from the randomized phase III KEYNOTE- ... Previous results of the phase 3 KEYNOTE-048 study showed that pembrolizumab significantly improved overall survival (OS) compared with cetuximab ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9902012/

Updated Results of the Phase III KEYNOTE-048 Study - PMC Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11590380/

Safety outcomes of pembrolizumab with platinum agent ... Strengths of this study do include the exclusion of non-squamous cell head and neck cancer histology along with utilization of a standard of care active ...

7. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/10781552231217686

Safety outcomes of pembrolizumab with platinum agent ... Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer.

8. ascopost.com ascopost.com/News/60093

First-Line Pembrolizumab for Recurrent or Metastatic Head ... Treatment with pembrolizumab/chemotherapy resulted in a median overall survival of 14.7 months vs 11.0 months with cetuximab/chemotherapy in ...