A Randomized Phase III Trial of Chemo-Immunotherapy vs Immunotherapy Alone for the Vulnerable Older Adult With Advanced Non-Small Cell Lung Cancer: The ACHIEVE Study

Plain English Summary

Chemotherapy Combined With Immunotherapy Versus Immunotherapy Alone for Older Adults With Stage IIIB-IV Lung Cancer, The ACHIEVE Trial is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Advanced Lung Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8. This trial tests if adding chemotherapy to immunotherapy is better than immunotherapy alone for advanced lung cancer in older adults. It is for patients aged 70 and older with specific types of non-small cell lung cancer that has spread. Participation involves being randomly assigned to one of two treatment groups and undergoing regular medical assessments. Standard treatments for advanced lung cancer include chemotherapy, immunotherapy, or targeted therapies, depending on the cancer's specific characteristics. The trial aims to enroll 304 participants.

Official Summary

This phase III trial compares the effect of adding chemotherapy to immunotherapy (pembrolizumab) versus immunotherapy alone in treating patients with stage IIIB-IV lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab and chemotherapy may help stabilize lung cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 70 or older and have been diagnosed with non-small cell lung cancer that is stage IIIB, IIIC, or IV. Your cancer must have a specific marker (PD-L1 TPS of 1-49%) and not have certain genetic mutations that can be treated with oral medications. You cannot join if you have active brain metastases or have previously received chemotherapy or immunotherapy for advanced disease, with some exceptions. Good general health, including specific blood counts and organ function, is required. This trial is studying Advanced Lung Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how long patients live overall, helping to determine if the combination treatment offers a survival benefit compared to immunotherapy alone. The specific primary outcome measures are: Overall survival (OS) (From randomization to death from any cause, and patients who are alive at the time of final analysis will be censored at the last date of contact, assessed up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to find a more effective treatment for vulnerable older adults with advanced lung cancer, addressing a need for better options in this specific patient group. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Advanced Lung Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This Phase III trial, sponsored by the NCI, investigates a common treatment approach for advanced lung cancer, suggesting potential for improved outcomes if successful, which could influence future tr Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific lung cancer type and overall health. Understand that you will be randomly assigned to receive either chemotherapy plus immunotherapy or immunotherapy alone. Be prepared for regular clinic visits for treatment, monitoring, and assessments of your health and cancer status. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 304 participants

Interventions

• DRUG: Carboplatin — Given IV
• PROCEDURE: Computed Tomography — Undergo CT scan
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI
• DRUG: Nab-paclitaxel — Given IV
• DRUG: Paclitaxel — Given IV

Primary Outcomes

• Overall survival (OS) (From randomization to death from any cause, and patients who are alive at the time of final analysis will be censored at the last date of contact, assessed up to 5 years)

Secondary Outcomes

• Progression free survival (PFS) (From randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or death from any cause, whichever occurs first, assessed up to 5 years)
• Six month PFS (From randomization to documented disease progression per RECIST 1.1 or death from any cause, whichever occurs first, assessed at 6 months)
• Best objective response (Up to 5 years)
• Incidence of adverse events (Up to 2 years)
• Evaluation of quality of life (QOL) measures (Baseline up to 6 months)

Full Eligibility Criteria

Inclusion Criteria:

* STEP 1 REGISTRATION
* Patient must be ≥ 70 years of age
* Patient must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with PD-L1 Tumor Proportion Score (TPS) range of 1-49%
* Patient must have Stage IIIB, IIIC or IV disease and not be candidates for combined chemo-radiation. NOTE: Prior chemo-radiation therapy (RT) for stage III with recurrence is allowed
* Patient must have a tumor that is negative for EGFR mutation/ALK translocations or other actionable first line mutations in which patients would receive first-line oral tyrosine kinase inhibitors
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2
* Patient must agree not to father children while on study and for 6 months after the last dose of protocol treatment
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Absolute neutrophil count (ANC) ≥ 1,500/uL (obtained within 14 days prior to Step 1 registration)
* Platelets ≥ 75,000/uL (obtained within 14 days prior to Step 1 registration)
* Hemoglobin (Hgb) ≥ 8.0 g/dL (obtained within 14 days prior to Step 1 registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to Step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3.0 × institutional ULN (obtained within 14 days prior to Step 1 registration)
* Creatinine clearance (CrCL) ≥ 45 mL/min (estimated using Cockcroft-Gault method with actual body weight or measured) (obtained within 14 days prior to Step 1 registration)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months of Step 1 registration are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have undetectable HCV viral
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must be English or Spanish speaking to be eligible for the QOL component of the study

  * NOTE: Sites cannot translate the associated GA or QOL forms
* Patient must not have symptomatic central nervous system disease (CNS) metastases. Patients with a clinical history of CNS metastases or cord compression are eligible if they have been definitively treated and are clinically stable for at least 14 days prior to Step 1 registration and off all steroids for at least 24 hours prior to Step 1 registration. Patients with asymptomatic CNS metastases are eligible
* Patient must not have had any prior cytotoxic chemotherapy regimen for metastatic disease. Chemotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed, and they have fully recovered from treatment related adverse events prior to Step 1 registration
* Patient must not have had any prior immunotherapy for metastatic disease. Immunotherapy given in the setting of adjuvant therapy or locally advanced disease is allowed as long as treatment was completed greater than 6 months prior to Step 1 registration
* Patient must not have a history of uncontrolled autoimmune conditions with the following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis, psoriasis/psoriatic arthritis, Hashimoto's thyroiditis, lupus, inflammatory bowel disease
* Patient must not be on immunosuppressive medication, including steroids (if doses exceed the equivalent of prednisone 10 mg daily). Short courses of steroids which are discontinued prior to randomization are acceptable. Patients on inhaled, intranasal and/or topical steroids are eligible
* Patient must have baseline imaging done assessing all measurable or non-measurable sites of disease within 45 days prior to Step 1 registration
* Investigator must declare their intended chemotherapy regimen should their patient be randomized to Arm B (doublet versus\[vs\] singlet)
* STEP 2 RANDOMIZATION
* Patient must have completed the baseline Geriatric Assessment (GA) after Step 1 registration and prior to Step 2 randomization

Trial Locations

• Highlands Oncology Group - Fayetteville, Fayetteville, Arkansas, United States
• Mercy Hospital Fort Smith, Fort Smith, Arkansas, United States
• Highlands Oncology Group - Rogers, Rogers, Arkansas, United States
• Highlands Oncology Group, Springdale, Arkansas, United States
• Kaiser Permanente Dublin, Dublin, California, United States
• Kaiser Permanente-Fremont, Fremont, California, United States
• Kaiser Permanente Fresno Orchard Plaza, Fresno, California, United States
• Kaiser Permanente-Fresno, Fresno, California, United States
• Kaiser Permanente- Modesto MOB II, Modesto, California, United States
• Kaiser Permanente-Modesto, Modesto, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Stage IIIB Lung Cancer
• Stage IIIC Lung Cancer
• Stage IV Lung Cancer
• Advanced Lung Cancer
• Cancer
• Oncology
• Immunotherapy
• Chemotherapy

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