Immunotherapy Combinations for Non-Small Cell Lung Cancer

(Morpheus Lung Trial)

Recruiting at 43 trial locations

Overseen By Reference Study ID Number: BO39610 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Disqualifiers: Autoimmune disease, CNS metastases, Pneumonitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

314 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug combination Atezolizumab, Carboplatin, and Pemetrexed for treating non-small cell lung cancer?

Research shows that combining pembrolizumab with pemetrexed and a platinum-based drug significantly improves survival in non-small cell lung cancer patients, suggesting that similar combinations, like atezolizumab with carboplatin and pemetrexed, may also be effective. ^{1 2 3 4 5}

Is the combination of immunotherapy and chemotherapy safe for treating non-small cell lung cancer?

Research shows that combining immunotherapy drugs like pembrolizumab and atezolizumab with chemotherapy drugs such as pemetrexed and carboplatin is generally safe for treating non-small cell lung cancer, though some patients may experience side effects. These side effects can vary in severity, and taking supplements like folic acid and vitamin B12 can help improve safety without reducing effectiveness. ^{2 5 6 7 8}

What makes the drug combination of Atezolizumab, Carboplatin, and Pemetrexed unique for treating non-small cell lung cancer?

This drug combination is unique because it combines immunotherapy (Atezolizumab) with chemotherapy (Carboplatin and Pemetrexed), offering an effective first-line treatment option for non-small cell lung cancer regardless of PD-L1 expression, which is a protein that can affect how well the immune system can attack cancer cells. ^{2 3 5 9 10}

What is the purpose of this trial?

This study will evaluate the efficacy, safety, and pharmacokinetics of immunotherapy-based treatment combinations in participants with metastatic non-small cell lung cancer (NSCLC). Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of participants with tumor PD-L1 expression who have received no prior systemic therapy for metastatic NSCLC, and Cohort 2 will consist of participants who experienced disease progression during or following treatment with a platinum-containing regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as one line of therapy or as two separate lines of therapy, regardless of PD-L1 expression. In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). Participants who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment regimen (Stage 2).

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with metastatic non-small cell lung cancer. Cohort 1 includes those who haven't had systemic therapy and have high PD-L1 in tumors. Cohort 2 has patients whose disease progressed after platinum-based and PD-L1/PD-1 inhibitor treatments. Participants must be able to perform daily activities with minimal assistance, have a life expectancy of at least 3 months, measurable disease, proper organ function, and agree to use contraception.

Inclusion Criteria

My blood and organs are functioning well.

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating eggs as outlined for each specific treatment arm

My lung cancer is confirmed to be non-small cell type and has spread.

Exclusion Criteria

I have a history of certain lung conditions or signs of lung inflammation on a chest scan.

I frequently need procedures to remove excess fluid from my body.

I have brain metastases that are untreated or getting worse.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage 1

Participants receive various immunotherapy-based treatment combinations until unacceptable toxicity or loss of clinical benefit

Variable (cycle length 21-28 days)

Treatment Stage 2

Participants who experience disease progression or loss of clinical benefit in Stage 1 may continue treatment with a different regimen

Variable (cycle length 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Pemetrexed
• Radiation

Trial Overview The study tests various immunotherapy combinations on two groups: one untreated for metastatic NSCLC (high tumor PD-L1 expression), the other previously treated but progressed. It assesses effectiveness, safety, and drug behavior in the body over two stages—initial treatment followed by an alternative if needed due to progression or side effects.

Participant Groups

Group I: Stage 2: Cohort 2: Atezolizumab + RO6958688 Experimental Treatment 3 Interventions

Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group II: Stage 2: Cohort 2: Atezolizumab + Linagliptin Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Linagliptin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group III: Stage 2: Cohort 2: Atezolizumab + Docetaxel Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who have received treatment with Atezolizumab + Docetaxel in Stage 1 will not receive this treatment in Stage 2.

Group IV: Stage 2: Cohort 1: Atezolizumab + Pemetrexed + Carboplatin Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Pemetrexed + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group V: Stage 2: Cohort 1: Atezolizumab + Gemcitabine + Carboplatin Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Gemcitabine + Carboplatin arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group VI: Stage 1: Cohort 2: Atezolizumab + Sacituzumab Govitecan Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Sacituzumab Govitecan arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group VII: Stage 1: Cohort 2: Atezolizumab + RO6958688 Experimental Treatment 3 Interventions

Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group VIII: Stage 1: Cohort 2: Atezolizumab + Ipatasertib Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Ipatasertib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group IX: Stage 1: Cohort 2: Atezolizumab + Evolocumab Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Evolocumab arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit.

Group X: Stage 1: Cohort 2: Atezolizumab + Docetaxel Experimental Treatment 2 Interventions

Participants in Atezolizumab + Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group XI: Stage 1: Cohort 2: Atezolizumab + Cobimetinib Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin, Atezolizumab + Gemcitabine + Carboplatin, Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group XII: Stage 1: Cohort 2: Atezolizumab + Camonsertib Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Camonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group XIII: Stage 1: Cohort 2: Atezolizumab + CPI-444 Experimental Treatment 2 Interventions

Participants in the Atezolizumab + CPI-444 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group XIV: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Tiragolumab Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Bevacizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group XV: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Radiotherapy Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Bevacizumab + Radioatherapy arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group XVI: Stage 1: Cohort 2: Atezolizumab + Bevacizumab + Camonsertib Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Bevacizumab + Comonsertib arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group XVII: Stage 1: Cohort 2: Atezolizumab + Bevacizumab Experimental Treatment 2 Interventions

Participants in Atezolizumab + Bevacizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group XVIII: Stage 1: Cohort 1: Atezolizumab + Tiragolumab + XL092 (Zanzalintinib) Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Tiragolumab + XL092 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group XIX: Stage 1: Cohort 1: Atezolizumab + RO6958688 Experimental Treatment 3 Interventions

Participants in the Atezolizumab + RO6958688 arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria. Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + Docetaxel treatment or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group XX: Stage 1: Cohort 1: Atezolizumab + Cobimetinib Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Cobimetinib arm will receive treatment (cycle length 28 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on 1L treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria. Participants who progressed on 2L/3L treatment, may have the option of receiving Atezolizumab + RO6958688, Atezolizumab + Docetaxel or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group XXI: Stage 1: Cohort 2: Docetaxel Active Control 1 Intervention

Participants in the Docetaxel arm will receive treatment (cycle length 21 days) until unacceptable toxicity or disease progression. Participants who progressed on treatment may have the option of receiving Atezolizumab + RO6958688 or Atezolizumab + Linagliptin treatment, provided they meet the eligibility criteria.

Group XXII: Stage 1: Cohort 1: Atezolizumab + Tiragolumab Active Control 2 Interventions

Participants in the Atezolizumab + Tiragolumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit.

Group XXIII: Stage 1: Cohort 1: Atezolizumab Active Control 1 Intervention

Participants in the Atezolizumab arm will receive treatment (cycle length 21 days) until unacceptable toxicity or loss of clinical benefit. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Pemetrexed + Carboplatin or Atezolizumab + Gemcitabine + Carboplatin treatment, provided they meet the eligibility criteria.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

Findings from Research

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]

The ANTELOPE trial is a phase II study comparing the efficacy of a pemetrexed-free regimen (atezolizumab, carboplatin, and nab-paclitaxel) against a pemetrexed-based regimen (pembrolizumab, cis-/carboplatin, and pemetrexed) in treating TTF-1 negative non-small cell lung adenocarcinoma (NSCLC/ADC).

This trial aims to enroll 136 participants across 30 sites in Germany, focusing on overall survival as the primary endpoint, which will help determine the best treatment approach for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). Frost, N., Bleckmann, A., Griesinger, F., 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]

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 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]

The combination of pemetrexed, platinum, and pembrolizumab shows manageable toxicity, with most severe adverse events occurring early in treatment and resolving within two weeks, indicating a favorable safety profile for long-term use.

While there was a slightly higher incidence of renal toxicity in patients receiving the pembrolizumab combination compared to those on pemetrexed alone, this did not increase with longer treatment durations, supporting the regimen's safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. Garon, EB., Aerts, J., Kim, JS., et al.[2023]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Pemetrexed is a multitargeted antifolate that effectively inhibits key enzymes in the folate pathway, showing clinical activity in non-small-cell lung cancer (NSCLC) and various other solid tumors.

The addition of low-level folic acid and vitamin B12 supplements enhances the safety of pemetrexed treatment without reducing its effectiveness against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Molina, JR., Adjei, AA.[2015]

Immunotherapy, particularly with pembrolizumab or atezolizumab combined with platinum-based chemotherapy, has become an effective first-line treatment for advanced non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels.

Patients with negative PD-L1 expression and low tumor mutational burden (TMB) may not benefit from immunotherapy combinations and might be better treated with traditional platinum-based chemotherapy, highlighting the need for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. Proto, C., Ferrara, R., Signorelli, D., et al.[2019]

In a study of 114 patients with advanced nonsquamous non-small cell lung cancer (NSCLC) negative for PD-L1, the combination of antiangiogenic therapy (bevacizumab) and chemotherapy resulted in a longer median progression-free survival (PFS) of 9.8 months compared to 6.7 months for those receiving anti-PD-L1 monoclonal antibodies plus chemotherapy.

Overall survival (OS) also favored the antiangiogenic group, although not statistically significant, indicating that bevacizumab plus chemotherapy may be a more effective first-line treatment for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy or antiangiogenic therapy plus chemotherapy as first-line treatment of patients with PD-L1(-) advanced non-squamous non-small cell lung cancer in a Chinese cohort. Xia, R., Li, Y., Yang, L., et al.[2023]

References

1. Switzerland 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. [2023]

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

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). [2023]

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

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

4. United States 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. [2021]

5. China 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). [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

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

The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. [2015]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. [2019]

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

Immunotherapy or antiangiogenic therapy plus chemotherapy as first-line treatment of patients with PD-L1(-) advanced non-squamous non-small cell lung cancer in a Chinese cohort. [2023]