Combining Pembrolizumab, Bevacizumab, and Chemotherapy for Advanced Lung Cancer with ALK Mutation

Bevacizumab and Chemotherapy With or Without Pembrolizumab in First Line Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma Patients With Persistent 5'ALK: A Phase II Randmized Control Trial

This study is testing a new combination of two drugs and chemotherapy to see if it helps people with advanced lung cancer that has an ALK mutation and hasn't improved with another treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hunan Province Tumor Hospital (Academic / other)
• Drugs / interventions: Alectinib, radiation, Pembrolizumab, Bevacizumab, Chemotherapy
• Locations: 1 site (Changsha, Hunan)
• Trial ID: NCT05266846 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the safety and efficacy of Pembrolizumab and Bevacizumab in combination with chemotherapy for patients with advanced lung adenocarcinoma that has an ALK gene mutation and has not responded to Alectinib. The study involves administering Pembrolizumab and Bevacizumab along with chemotherapy agents Pemetrexed and Carboplatin over multiple cycles. Patients will be monitored for progression-free survival and overall response to the treatment. The trial aims to gather data on the effectiveness of this combination therapy in a specific patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with Stage IV ALK-rearranged lung adenocarcinoma that has persisted after treatment with Alectinib.

Not a fit: Patients with active central nervous system metastases or other malignancies within the past five years may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with ALK-rearranged lung cancer who have failed prior therapies.

How similar studies have performed: While this approach is novel in this specific context, similar combinations of immunotherapy and chemotherapy have shown promise in other studies.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years of age on day of signing informed consent.

  * Stage IV ALK-rearranged Lung Adenocarcinoma Persistent with 5'ALK Failed from first line Alectinib

    * Have at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator radiology review. Lesions that appear measurable, but have undergone palliative irradiation, cannot be target lesions ④20 FFPE sliders prepared,Subjects who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample ⑤Eastern Cooperative Oncology Group performance status 0 or 1

      * Life expectancy ≥3 months

        * Adequate hematologic and end organ function

Exclusion Criteria:

Cancer-Specific Exclusions:

①Active or untreated central nervous system metastases

②Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome

General Medical Exclusions:

* Pregnant or lactating women.

  * Has active autoimmune disease that has required systemic treatment in the past 2 years.

    * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

      * Positive test for human immunodeficiency virus.

        ⑤Active hepatitis B or hepatitis C.

        ⑥Severe infection within 4 weeks prior to randomization .

        ⑦Significant cardiovascular disease.

        ⑧Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures.

        ⑨Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment for another health-related problem.

Exclusion Criteria Related to Medications: Prior treatment with anti-programmed death-1, anti-PD-L1 therapeutic antibodies，and anti-VEGF agents.

Where this trial is running

Changsha, Hunan

• Hunan Cancer Hospital — Changsha, Hunan, China (Recruiting)

Study contacts

• Principal investigator: Yongchang C Zhang, MD — Hunan Cancer Hospital
• Study coordinator: Yongchang C Zhang, MD

Conditions ALK Gene Mutation; Lung Adenocarcinoma; Immunotherapy