Tobemstomig + Chemotherapy vs Pembrolizumab + Chemotherapy for Lung Cancer

Not currently recruiting at 95 trial locations

Overseen By Reference Study ID Number: BO44178 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Antibiotics, Immunosuppressants, Immunostimulants, others

Disqualifiers: EGFR mutation, ALK fusion, Autoimmune disease, CNS metastases, 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: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new lung cancer treatment, tobemstomig (an experimental treatment), combined with chemotherapy. The goal is to determine if this combination is more effective than the current standard treatment, pembrolizumab with chemotherapy, for individuals with advanced non-small-cell lung cancer (NSCLC) that cannot be surgically removed. Participants must have untreated, advanced NSCLC and be ineligible for surgery or combined chemotherapy and radiation. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer therapy, including hormonal therapy, at least 21 days before starting the study treatment. Additionally, you must not be on systemic immunosuppressive medication within 2 weeks prior to starting the study treatment.

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

Research shows that tobemstomig, a new treatment under study, has generally been well-tolerated in early research. These initial studies focused on determining the right dose and assessing its safety for people with solid tumors. While no major safety issues emerged, more information is needed to fully understand its safety.

In contrast, pembrolizumab, which is being compared in the trial, has a proven track record. It has been used to treat lung cancer for several years. Research has shown it is generally safe when combined with chemotherapy and has been linked to a 5-year survival benefit in patients with non-small-cell lung cancer (NSCLC).

Since this trial is in an early phase, tobemstomig is still undergoing safety testing. However, pembrolizumab is already known to be safe in similar situations. These findings can help prospective participants understand the safety of both treatments being studied. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for lung cancer, which often includes drugs like pembrolizumab paired with chemotherapy, Tobemstomig represents a new approach. Researchers are excited about Tobemstomig because it is an innovative treatment option that combines a novel active ingredient with chemotherapy. This combination could potentially enhance the effectiveness of the treatment by targeting cancer cells in a unique way. By introducing this new mechanism of action, Tobemstomig aims to improve outcomes for patients with non-squamous and squamous non-small cell lung cancer (NSCLC).

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

This trial will compare two treatment options for non-small-cell lung cancer (NSCLC): pembrolizumab combined with chemotherapy and tobemstomig combined with chemotherapy. Research has shown that combining pembrolizumab with chemotherapy can extend the lives of patients with NSCLC. Specifically, studies found that patients lived for a median of 19.2 months, and about 25% were still alive five years after starting treatment.

For tobemstomig, a newer treatment option in this trial, early trials are examining its ability to help the immune system find and attack cancer cells. Tobemstomig targets two proteins, PD-1 and LAG-3, which usually help cancer hide from the immune system. Initial results are promising, suggesting that tobemstomig might enhance the immune response against cancer, but more research is needed to confirm its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-LaRoche

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who haven't had treatment yet. They should have a life expectancy of at least 12 weeks, no HIV or hepatitis, good heart function, and be generally well enough to perform daily activities with ease (ECOG status 0-1). People can't join if they've had certain other cancers recently, autoimmune diseases, organ transplants, severe infections or allergies related to the treatments being tested.

Inclusion Criteria

My cancer can be measured by tests.

We need to make sure we have a sample of your tumor tissue for testing.

I know my cancer's PD-L1 status.

Exclusion Criteria

I haven't had any cancer treatments, including hormone therapy, in the last 21 days.

I am allergic to certain medication ingredients, including those from Chinese hamster ovary cells.

I have active or untreated latent tuberculosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive induction treatment with either tobemstomig or pembrolizumab in combination with platinum-based chemotherapy for four 21-day cycles

12 weeks

4 visits (in-person, every 3 weeks)

Maintenance Therapy

Participants continue with maintenance therapy with either tobemstomig or pembrolizumab in combination with pemetrexed or paclitaxel until disease progression or treatment discontinuation

Until disease progression

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab
• Pemetrexed
• RO7247669

Trial Overview The study compares Tobemstomig combined with platinum-based chemotherapy against Pembrolizumab with the same chemo in patients with untreated NSCLC. It aims to see which combination works better and is safer while also checking how the body processes these drugs.

How Is the Trial Designed?

Group I: Arm A: Tobemstomig + Platinum-Based Chemotherapy Experimental Treatment 4 Interventions

Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded tobemstomig in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded tobemstomig together with pemetrexed until disease progression or treatment discontinuation. Participants with squamous (SQ) NSCLC will receive blinded tobemstomig in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded tobemstomig (on Day 1) Q3W until disease progression or treatment discontinuation.

Group II: Arm B: Pembrolizumab + Platinum-Based Chemotherapy Active Control 4 Interventions

Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation. Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

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]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

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]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

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]

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]

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., 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]

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NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

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