What is the mechanism of action of this treatment?

Durvalumab, a PD-L1 inhibitor, enhances the immune system's ability to attack cancer cells by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells. Pemetrexed, an antifolate chemotherapy, disrupts DNA and RNA synthesis by inhibiting key enzymes involved in nucleotide synthesis, preventing cancer cell replication. Carboplatin, a platinum-based chemotherapy, forms DNA crosslinks that inhibit DNA replication and transcription, leading to cell death. These treatments are crucial for Non-Small Cell Lung Cancer patients as they target different aspects of cancer cell survival and proliferation, providing a comprehensive approach to treatment.

What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) such as Durvalumab (PD-L1 inhibitor), Pemetrexed (antifolate chemotherapy), and Carboplatin (platinum-based chemotherapy) are associated with several side effects. Durvalumab can cause immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Pemetrexed is known for causing myelosuppression, fatigue, nausea, and mucositis. Carboplatin's side effects include myelosuppression, particularly thrombocytopenia, nephrotoxicity, neurotoxicity, and nausea. Combining these treatments can increase the risk and severity of these side effects, necessitating careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Small Cell Lung Cancer (NSCLC) that involve immune checkpoint inhibitors and platinum-based chemotherapies. Pembrolizumab, a PD-1 inhibitor, has been approved in combination with platinum-based chemotherapies such as carboplatin and paclitaxel or nab-paclitaxel for the first-line treatment of metastatic squamous NSCLC. Additionally, the combination of atezolizumab (a PD-L1 inhibitor) with carboplatin and paclitaxel has been approved for advanced nonsquamous NSCLC. These approvals highlight the efficacy of combining immune checkpoint inhibitors with platinum-based chemotherapies, similar to the combination of Durvalumab, Pemetrexed, and Carboplatin being studied in clinical trials.

What other types of research exist?

Promising alternatives to Durvalumab in combination with Pemetrexed and Carboplatin for NSCLC patients include: 1) Atezolizumab in combination with Bevacizumab, Pemetrexed, and Carboplatin, which has shown improvement in health-related quality of life and treatment tolerance. 2) Pembrolizumab in combination with Carboplatin and Pemetrexed, which has demonstrated promising results in phase II and III studies. 3) Sintilimab in combination with Pemetrexed and Platinum, which has shown promising efficacy in a phase 3 study.

← Back to Search

Chemotherapy

Chemo-Immunotherapy for Non-Small Cell Lung Cancer (STAGGER Trial)

Phase 2

Recruiting

Led By Wallace Akerley, MD

Research Sponsored by University of Utah

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG Performance Status ≤ 2

Histologically or cytologically confirmed metastatic non-squamous non-small cell lung cancer

Must not have

Current or prior use of immunosuppressive medication within 14 days of cycle one day one, EXCEPT for permitted steroids

Prior radiation therapy within 2 weeks prior to cycle one day one

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of an immune-boosting drug and chemotherapy in adults with advanced lung cancer. The treatment aims to help the immune system fight cancer while also killing cancer cells directly.

Who is the study for?

Adults with metastatic non-squamous non-small cell lung cancer who haven't had chemoimmunotherapy can join this trial. They must be willing to use effective birth control and follow the study's protocol, including visits and exams. People with certain health conditions or those on immunosuppressive medications (except some steroids) are excluded.

What is being tested?

The trial is testing two staggered dosing regimens of Durvalumab combined with Pemetrexed and Carboplatin in patients. It aims to determine which regimen is more effective for treating advanced lung cancer in a Phase II open label, randomized setting.

What are the potential side effects?

Durvalumab may cause immune-related side effects like inflammation of organs, fatigue, infusion reactions; Pemetrexed and Carboplatin can lead to blood count changes, nausea, kidney issues, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I can take care of myself and am up and about more than half of my waking hours.

Select...

My lung cancer is non-squamous and has spread to other areas.

Select...

I have not received chemoimmunotherapy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I haven't taken immunosuppressive drugs, except allowed steroids, in the last 14 days.

Select...

I have not had radiation therapy in the last 2 weeks.

Select...

I have or had an autoimmune or inflammatory disorder.

Select...

My lung cancer is non-squamous and has ALK or EGFR mutations.

Select...

I have not been diagnosed with any cancer other than my current one in the last 2 years.

Select...

My cancer has spread to my brain and is not under control.

Select...

I do not have any uncontrolled illnesses.

Select...

I have had cancer spread to the lining of my brain and spinal cord.

Select...

I do not have an active infection like TB, hepatitis B, or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Rate of clinical benefit

Secondary study objectives

Incidence of adverse events

Objective response rate (ORR)

Overall survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B: Immuno-ChemoExperimental Treatment3 Interventions

ArmB receives immunotherapy on D1 and chemotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.

Group II: Arm A: Chemo-ImmunoExperimental Treatment3 Interventions

ArmA receives chemotherapy on D1 and immunotherapy on D8 of a 28-day cycle for the first 2cycles. After the first 2cycles, patients on Arm A and Arm B will be administered chemotherapy and immunotherapy on D1 of a 21day cycle for cycles 3 and 4. After 4cycles of chemo-immunotherapy, patients receive maintenance therapy with durvalumab and pemetrexed until treatment discontinuation. Maintenance therapy is administered on D1 of a 21day cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pemetrexed

2014

Completed Phase 3

~5550

Carboplatin

2014

Completed Phase 3

~6120

Durvalumab

2017

Completed Phase 2

~3750

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Durvalumab, a PD-L1 inhibitor, enhances the immune system's ability to attack cancer cells by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells. Pemetrexed, an antifolate chemotherapy, disrupts DNA and RNA synthesis by inhibiting key enzymes involved in nucleotide synthesis, preventing cancer cell replication. Carboplatin, a platinum-based chemotherapy, forms DNA crosslinks that inhibit DNA replication and transcription, leading to cell death. These treatments are crucial for Non-Small Cell Lung Cancer patients as they target different aspects of cancer cell survival and proliferation, providing a comprehensive approach to treatment.

Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11).An unusual case of isolated peritoneal metastases from lung adenocarcinoma.