Chemotherapy + Bevacizumab +/- Immunotherapy for Advanced Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Joseph Treat, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Fox Chase Cancer Center

Must be taking: TKIs

Must not be taking: Immunomodulatory agents, Chemotherapy

Disqualifiers: Cirrhosis, Hypertension, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

While cigarette smoking remains the primary cause of most lung cancer cases, lung carcinoma in never smokers account for nearly 20 percent of cases. Never smokers with lung cancer typically present with different molecular profiles from that of smokers, which results in prognostic and therapeutic implications. Molecular changes in NSCLC that have therapeutic significance include mutations in the epidermal growth factor receptor (EGFR) and rearrangements in the anaplastic lymphoma kinase (ALK) gene. These driver mutations typically are present in lung tumors found in never or light smokers. The addition of bevacizumab to carboplatin and paclitaxel in first-line treatment of non-squamous NSCLC showed improved survival compared to carboplatin and paclitaxel alone, 12.3 vs. 10.3 months respectively. Results from the POINTBREAK trial demonstrated that carboplatin + pemetrexed + bevacizumab is an alternative option to carboplatin + paclitaxel + bevacizumab, with comparable survival but less toxicity. In recent years, immunotherapy has emerged as a form of treatment that can lead to robust responses in a subset of patients. The PD-1 inhibitor nivolumab and the PD-L1 inhibitor atezolizumab have shown prolonged survival in comparison to docetaxel in patients who previously progressed with chemotherapy, irrespective of PD-L1 expression. Thus, this study combines immunotherapeutic agent atezolozumab with an ant-angiogenic agent, bevacizumab, and double platinum therapy (carboplatin and pemetrexed).

Will I have to stop taking my current medications?

The trial requires a minimum washout period (time without taking certain medications) of 3 days for patients with EGFR mutations who have been on TKIs (targeted cancer therapies). Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of chemotherapy, bevacizumab, and immunotherapy for advanced non-small cell lung cancer?

Research shows that combining bevacizumab with chemotherapy, like pemetrexed and platinum-based drugs, has significant benefits for patients with advanced non-small cell lung cancer. Additionally, atezolizumab combined with bevacizumab and chemotherapy is considered a standard treatment, suggesting its effectiveness in improving patient outcomes. ^{1 2 3 4 5}

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

Research shows that the combination of chemotherapy drugs like carboplatin and pemetrexed with bevacizumab has been studied for safety in patients with advanced non-small cell lung cancer. These studies generally focus on how well patients tolerate the treatment and any side effects they experience, indicating that safety has been a key consideration in these trials. ^{6 7 8 9 10}

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

This drug combination is unique because it includes atezolizumab, an immunotherapy that helps the immune system fight cancer, along with bevacizumab, which targets blood vessels that supply the tumor, and traditional chemotherapy agents carboplatin and pemetrexed, offering a comprehensive approach to treating advanced non-small cell lung cancer. ^{3 6 11 12 13}

Eligibility Criteria

Adults over 18 with stage IV non-squamous NSCLC who haven't had chemo, anti-VEGF, or immunotherapy (except certain TKIs for EGFR mutations). Must have measurable disease, adequate organ function, and no serious health issues like uncontrolled hypertension or recent bleeding. Smokers must have specific EGFR mutations; never-smokers can join without these mutations.

Inclusion Criteria

I am fully active or can carry out light work.

I completed my curative therapy over a year ago.

I am willing to use birth control if I can have children.

Exclusion Criteria

I have had a severe hypertension crisis or brain issues due to high blood pressure.

I do not have any uncontrolled illnesses or infections that would affect my participation.

I am willing to switch from denosumab to a bisphosphonate for the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Carboplatin + Pemetrexed + Bevacizumab, with or without Atezolizumab

12.5 months

Maintenance

Participants continue with Pemetrexed + Bevacizumab, with or without Atezolizumab

15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• Bevacizumab (Monoclonal Antibodies)
• Carboplatin (Alkylating agents)
• Pemetrexed (Anti-metabolites)

Trial Overview This trial tests if adding Atezolizumab to Carboplatin+Pemetrexed+Bevacizumab improves outcomes in advanced lung cancer. Participants are randomly assigned to receive either the four-drug combo (Arm B) or just the three drugs without Atezolizumab (Arm A).

Participant Groups

Group I: Arm A Experimental Treatment 1 Intervention

Arm A: Carboplatin + Pemetrexed + Bevacizumab + Atezolizumab Maintenance: Pemetrexed + Bevacizumab + Atezolizumab

Group II: Arm B Active Control 1 Intervention

Arm B: Carboplatin + Pemetrexed + Bevacizumab Maintenance: Pemetrexed + Bevacizumab

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Fox Chase Cancer Center Philadelphia, PA

Who Is Running the Clinical Trial?

Fox Chase Cancer Center Lead Sponsor

National Comprehensive Cancer Network Collaborator

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Direct Comparison Between the Addition of Pembrolizumab or Bevacizumab for Chemotherapy-Based First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer Lacking Driver Mutations. [2022] The addition of bevacizumab or pembrolizumab to pemetrexed-platinum chemotherapy has produced significant clinical benefits to patients with untreated, advanced non-squamous non-small cell lung cancer (NSCLC) lacking targetable genetic aberrations. However, the direct comparison between these two first-line treatments needs to be investigated.

2. Thailand pubmed.ncbi.nlm.nih.gov

Clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer. [2022] To observe the clinical efficacy of bevacizumab concomitant with pemetrexed in patients with advanced non-small cell lung cancer (NSCLC).

3. China pubmed.ncbi.nlm.nih.gov

Bevacizumab plus platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer: a randomized, open-label phase 2 study (CLEAR). [2022] Atezolizumab combined with bevacizumab plus platinum-based chemotherapy is a standard treatment for advanced non-squamous non-small-cell lung cancer (nsNSCLC). We aimed to determine the most effective platinum-based combination, such that future studies with atezolizumab can be conducted to further improve patient outcomes.

4. 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] Pembrolizumab combined with chemotherapy is now first-line standard of care in advanced non-small cell lung cancer. This real-life study aimed to assess efficacy and safety of carboplatin-pemetrexed plus pembrolizumab in advanced non-squamous non-small cell lung cancer.

5. Ireland pubmed.ncbi.nlm.nih.gov

Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/-bevacizumab for the first-line treatment of non-squamous NSCLC: A matching-adjusted indirect comparison. [2021] Multiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical trials. This study indirectly compared the effectiveness of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations.

6. China pubmed.ncbi.nlm.nih.gov

[Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin in Patients with IIIa Lung Adenocarcinoma]. [2019] Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma.

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

Carboplatin/pemetrexed/bevacizumab in the treatment of patients with advanced non-small-cell lung cancer: a single-institution experience. [2022] The purpose of this study was to determine the efficacy and tolerability of carboplatin, pemetrexed, and bevacizumab in patients with advanced, nonsquamous non-small-cell lung cancer (NSCLC).

8. 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] This post hoc analysis assessed the safety of pemetrexed and platinum in combination with pembrolizumab, including time-to-onset and time-to-resolution of all-cause any-grade and grade ≥3 adverse events (AEs) and renal AEs.

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Pemetrexed versus gefitinib versus erlotinib in previously treated patients with non-small cell lung cancer. [2021] The efficacy and safety of pemetrexed, gefitinib, and erlotinib administration in previously treated patients with non-small cell lung cancer (NSCLC) were compared.

10. England pubmed.ncbi.nlm.nih.gov

Phase II trial of pemetrexed disodium (ALIMTA, LY231514) in chemotherapy-naïve patients with advanced non-small-cell lung cancer. [2022] To evaluate the efficacy and safety of pemetrexed therapy for chemotherapy-naïve patients with surgically incurable non-small-cell lung cancer (NSCLC).

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

Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. [2022] Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non-small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting.

12. Ireland pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of bevacizumab versus pemetrexed for advanced non-squamous NSCLC in Italy. [2022] The new targeted agent bevacizumab in combination with cisplatin and gemcitabine (BCG), and a third-generation chemotherapy pemetrexed in combination with cisplatin (PC), are approved as first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC).

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

Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell Lung Cancer. [2021] Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non-small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC.