Vudalimab or Pembrolizumab with Chemotherapy for Lung Cancer

Recruiting at 48 trial locations

Overseen By Michael Chiarella

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Xencor, Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: CNS metastases, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days for initial dose determination, followed by up to 1.4 years

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of two treatments combined with chemotherapy for nonsquamous non-small cell lung cancer (NSCLC). One group receives vudalimab, an experimental drug, while the other receives pembrolizumab, both alongside standard chemotherapy. The researchers aim to determine the best dose of vudalimab and compare its results with pembrolizumab. Suitable participants have NSCLC without certain gene mutations, have not received prior treatment for advanced cancer, and are generally in good health aside from their cancer. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications like corticosteroids or other immunosuppressive drugs, you may need to stop them at least 14 days before starting the study drug.

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

Earlier studies have shown that the combination of pembrolizumab and chemotherapy has promising safety results. Long-term data indicate that this combination did not introduce any new safety issues. Patients tolerated it well, and survival benefits appeared over several years.

Research on vudalimab is less extensive, but early results are encouraging. These studies aim to determine the best dose when vudalimab is combined with chemotherapy. Although more data is needed, the research so far suggests it is generally well-tolerated.

Both treatments undergo careful testing to ensure safety for people with non-small cell lung cancer. Safety remains a top priority, and the studies are designed to closely monitor any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Vudalimab because it represents a new approach to treating lung cancer. Unlike most treatments that focus on common pathways, Vudalimab is an investigational antibody designed to block specific immune checkpoints, potentially enhancing the body's immune response against cancer cells. This could offer a fresh option alongside standard treatments like Pembrolizumab, which also boosts the immune system but through different pathways. By combining Vudalimab with chemotherapy agents like Carboplatin and Pemetrexed, there is hope for improved outcomes in patients who may not respond as well to existing therapies.

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

In this trial, participants will receive either pembrolizumab or vudalimab combined with chemotherapy. Research has shown that combining pembrolizumab with chemotherapy can extend the lives of patients with non-small cell lung cancer (NSCLC). Specifically, one study found that about 19% of patients using this combination were still alive after five years, outperforming chemotherapy alone.

For vudalimab, another treatment option in this trial, less information is available because it is a newer treatment under investigation. Like pembrolizumab, it targets certain proteins in the immune system, offering hope for effectiveness. Early indications suggest it could be beneficial, particularly when used with chemotherapy. ^{3 4 6 7 8}

Who Is on the Research Team?

Jolene Shorr

Principal Investigator

Executive Director, Clinical Development

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-squamous NSCLC who haven't had treatment before. They should not have certain gene mutations or a high PD-L1 level, and must be in good physical condition with a life expectancy of at least 3 months. Their liver, kidney, thyroid, and bone marrow must function well.

Inclusion Criteria

My lung cancer is advanced, cannot be surgically removed, and is not squamous type.

My liver, kidneys, thyroid, and bone marrow are working well.

You are expected to live for at least 3 more months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vudalimab or pembrolizumab in combination with chemotherapy as first-line treatment

21 days for initial dose determination, followed by up to 1.4 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1.4 to 2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Pembrolizumab
• Pemetrexed
• Vudalimab

Trial Overview

The study tests Vudalimab combined with chemotherapy (Carboplatin + Pemetrexed) against Pembrolizumab with the same chemo as first-line treatments. Part 1 determines the best dose of Vudalimab; Part 2 compares its effectiveness and safety to Pembrolizumab.

How Is the Trial Designed?

Group I: Vudalimab + Carboplatin + Pemetrexed Experimental Treatment 1 Intervention

Group II: Pembrolizumab + Carboplatin + Pemetrexed Active Control 1 Intervention

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

Published Research Related to This Trial

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 long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., 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]

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]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., 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 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]

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]

Citations

1.

merck.com

merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ...

Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8636217/

The 5‐year outcomes of the KEYNOTE‐024 trial

Pembrolizumab monotherapy could provide meaningful improved patient outcomes over platinum‐based chemotherapy for advanced NSCLC patients with PD‐L1 TPS ≥ 50%.

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.21.02885

Five-Year Outcomes With Pembrolizumab Versus ...

With 5-year OS rates of up to 22%, these data support the continued use of pembrolizumab monotherapy as a standard-of-care treatment for ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1801005

Pembrolizumab plus Chemotherapy in Metastatic Non– ...

Treatment Patterns and Outcomes of Non-Small Cell Lung Cancer with High PD-L1 Expression using Real World Evidence, Clinical Lung Cancer, 26 ...

5.

nature.com

nature.com/articles/s41416-024-02895-1

Real-world evidence for pembrolizumab in non-small cell ...

Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02578680

NCT02578680 | Study of Pemetrexed+Platinum ...

This is an efficacy and safety study of pembrolizumab (MK-3475) combined with pemetrexed/platinum chemotherapy versus pemetrexed/platinum chemotherapy alone

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10082311/

5-Year Outcomes From the Phase 3 KEYNOTE-189 Study - PMC

These data support the feasibility of a 2-year treatment duration with pembrolizumab plus pemetrexed-platinum and are consistent with the outcomes reported in ...

8.

tlcr.amegroups.org

tlcr.amegroups.org/article/view/72682/html

Pembrolizumab plus pemetrexed-carboplatin combination in ...

With median progression-free survival and overall survival of 9.0 and 20.6 months, respectively and no new safety signal, our real-life data are ...