Carboplatin + Pemetrexed + Atezolizumab for Lung Cancer

Overseen By Danielle Bednarz, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Liza Villaruz, MD

Must not be taking: Immunosuppressants, Anti-epileptics

Disqualifiers: Autoimmune disease, Cardiovascular disease, 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

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

Compensation: Varies

Number of Visits: 3

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a drug combination, including atezolizumab (an immunotherapy drug), tiragolumab, and chemotherapy, for treating advanced lung cancer that has spread to the brain but isn't causing symptoms. The main goal is to determine if these treatments can manage non-squamous non-small cell lung cancer (NSCLC) in patients with specific brain metastases (tumors in the brain). Suitable candidates for this trial have NSCLC, specific brain tumors, and have not received other treatments for metastatic disease. As a Phase 2 trial, this 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 does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive medication or certain other treatments, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research is examining the safety and effectiveness of a combination of four drugs—tiragolumab, atezolizumab, carboplatin, and pemetrexed—for treating lung cancer. Earlier studies have shown that most patients tolerate this treatment well. Common side effects include fatigue, nausea, and reduced appetite. Serious side effects are less common but can occur. It's important to note that this treatment remains under study, so researchers continue to learn about its safety. Prospective trial participants should discuss potential risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tiragolumab with Atezolizumab, Carboplatin, and Pemetrexed for lung cancer because it introduces a new mechanism of action. Tiragolumab is an innovative therapy that targets TIGIT, a protein involved in suppressing the immune response against cancer cells. By blocking TIGIT, Tiragolumab may enhance the body's ability to fight cancer alongside Atezolizumab, which targets another protein called PD-L1. This dual approach could potentially improve the effectiveness of treatments compared to standard options that primarily focus on either PD-L1 or chemotherapy alone.

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

Research shows that using atezolizumab with carboplatin and pemetrexed may help treat advanced nonsquamous non-small cell lung cancer (NSCLC) that has spread to the brain and remains untreated. This combination has effectively managed the cancer for many patients. In this trial, participants will receive a combination that includes tiragolumab alongside atezolizumab, pemetrexed, and carboplatin. Researchers have investigated adding tiragolumab to see if it enhances the treatment's effectiveness. Some studies found that tiragolumab did not provide extra benefits beyond the atezolizumab and chemotherapy combination. However, most patients tolerate this treatment without serious side effects. Ongoing research explores whether tiragolumab might be more beneficial for certain conditions or specific patient groups. ^{1 2 6 7 8}

Who Is on the Research Team?

Liza C. Villaruz

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with non-squamous NSCLC and untreated brain metastases. Participants must have normal organ function, no recent severe infections or surgeries, and not be on systemic immunosuppressants. They should agree to contraception if of childbearing potential and can't join if they've had certain treatments for metastatic disease or have specific viral infections.

Inclusion Criteria

I have had radiation for cancer spread outside the brain with the goal of easing symptoms.

Ability to understand and the willingness to sign a written informed consent document.

I had treatment for early-stage lung cancer over a year ago.

Exclusion Criteria

I haven't had major surgery in the last 4 weeks and don't expect to need one during the study.

I have had lung issues like fibrosis or pneumonia, but not from radiation.

I don't have any health issues that would make it unsafe for me to take a new drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tiragolumab in combination with atezolizumab, pemetrexed, and carboplatin. On-treatment brain MRI at three weeks for safety purposes.

18 weeks

Regular visits including MRI at 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Restaging occurs at nine-week intervals.

Up to 5 years

Extension/Long-term follow-up

Participants are monitored for progression-free survival and overall survival.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Pemetrexed
• Tiragolumab

Trial Overview The study tests the combination of tiragolumab with carboplatin, pemetrexed, and atezolizumab in treating metastatic non-squamous NSCLC patients who also have asymptomatic brain metastases. It aims to assess safety and how well this combination works as a first-line treatment.

How Is the Trial Designed?

Group I: Single Treatment Arm Experimental Treatment 4 Interventions

Tiragolumab in combination with atezolizumab, pemetrexed, and carboplatin.

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?

Liza Villaruz, MD

Lead Sponsor

Trials

4

Recruited

40+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

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 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 a study of 109 patients with advanced non-squamous non-small cell lung cancer, the combination of pemetrexed and carboplatin followed by pemetrexed maintenance showed similar efficacy in elderly patients (≥70 years) compared to younger patients, with median progression-free survival of 5.2 months for the elderly versus 5.8 months for younger patients.

While elderly patients experienced more frequent grade 3/4 hematologic toxicities, these were manageable through dose adjustments, and non-hematologic toxicities were similar to those seen in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed and carboplatin combination therapy followed by pemetrexed maintenance in Japanese patients with non-squamous non-small cell lung cancer: A subgroup analysis of elderly patients. Nogami, N., Nishio, M., Okamoto, I., et al.[2022]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04619797

NCT04619797 | A Study of Tiragolumab in Combination ... The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37976444/

SKYSCRAPER-02: Tiragolumab in Combination ... - PubMed Tiragolumab did not provide additional benefit over atezolizumab and CE in untreated ES-SCLC. The combination was well tolerated with no new ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09259

Tiragolumab with Carboplatin, Pemetrexed, and ... This phase II trial studies the safety and effectiveness of tiragolumab in combination with carboplatin, pemetrexed, and atezolizumab in treating patients ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37603816/

Phase II Trial of Atezolizumab Combined With Carboplatin ... Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an ...

5. forpatients.roche.com forpatients.roche.com/content/patient-platform/global/en/trials/cancer/lung-cancer/a-study-of-tiragolumab-in-combination-with-atezolizumab-98469.pdf

A study of tiragolumab in combination with atezolizumab plus The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of tiragolumab in combination with atezolizumab plus pemetrexed and ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05746481/carboplatin-pemetrexed-and-atezolizumab-in-patients-with-non-squamous-non-small-cell-lung-cancer-nsclc-and-untreated-brain-metastases

Tiragolumab and Atezolizumab in Patients with Non- ... This is a phase II clinical trial aimed at the evaluation of the safety and clinical activity of tiragolumab in combination with atezolizumab ...

7. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2023/10/30858-Tiragolumab-Atezolizumab-for-Non-Small-Cell-Lung-Cancer-V1.0-OCT2023-NON-CONF.pdf

Health Technology Briefing October 2023 Tiragolumab in combination with atezolizumab, pemetrexed and carboplatin or cisplatin is currently in clinical development for patients with ...

8. onclive.com onclive.com/view/tiragolumab-plus-atezolizumab-chemo-misses-survival-end-points-in-metastatic-nonsquamous-nsclc

Tiragolumab Plus Atezolizumab/Chemo Misses Survival ... First-line tiragolumab plus atezolizumab and chemotherapy failed to improve survival in advanced nonsquamous non–small cell lung cancer.