Immunotherapy Combo for Lung Cancer (PACIFIC-8 Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally advanced (Stage III), unresectable NSCLC whose disease has not progressed following definitive platinum-based cCRT.
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop your current medications. However, you cannot use immunosuppressive medication within 14 days before the first dose of durvalumab.
Is the drug combination of Domvanalimab and Durvalumab promising for lung cancer?Yes, the combination of Domvanalimab and Durvalumab is promising for lung cancer. Durvalumab has shown to improve survival and enhance the body's immune response against cancer cells. It has been effective in treating various cancers, including lung cancer, especially when used with other treatments.127910
What safety data is available for the immunotherapy treatment involving durvalumab?Durvalumab, also known as MEDI4736 or Imfinzi, has been evaluated for safety in various studies. It is a PD-L1 inhibitor used in treating solid tumors, including non-small-cell lung cancer (NSCLC). Safety data indicates that durvalumab has a manageable safety profile, but it is associated with immune-related adverse effects (irAEs), such as pneumonitis, which is a serious and potentially fatal complication. The incidence of pneumonitis has been specifically studied in real-world settings to assess its occurrence in patients receiving durvalumab for NSCLC.23468
What data supports the idea that Immunotherapy Combo for Lung Cancer is an effective treatment?The available research shows that the Immunotherapy Combo for Lung Cancer, which includes durvalumab, is effective in treating non-small-cell lung cancer. In the POSEIDON study, combining durvalumab with another drug and chemotherapy improved how long patients lived and delayed the worsening of their cancer compared to just using chemotherapy. Additionally, durvalumab alone showed positive results in patients with advanced non-small-cell lung cancer, especially those with higher levels of a specific protein (PD-L1) on their cancer cells. This suggests that the Immunotherapy Combo can be more effective than traditional chemotherapy alone.234510
Eligibility Criteria
Adults with Stage III unresectable NSCLC who haven't progressed after platinum-based chemoradiation can join. They need a PD-L1 status ≥ 1%, adequate organ function, and no history of certain cancers or autoimmune diseases. Participants must be over 18, have completed at least two cycles of chemo with radiation, and not have used immunosuppressive drugs recently.Inclusion Criteria
My lung cancer was confirmed by lab tests and treated with chemo and radiation for stage III.
My condition did not worsen after receiving specific chemotherapy and radiation together.
My cancer does not have mutations in the EGFR or ALK genes.
I have completed at least 2 cycles of chemotherapy with platinum drugs and radiation.
My organs and bone marrow are working well.
I am fully active or restricted in physically strenuous activity but can do light work.
My tumor's PD-L1 status is 1% or higher.
I am 18 years old or older.
I received a specific dose of radiation as part of my treatment.
Exclusion Criteria
I haven't taken immunosuppressive drugs in the last 14 days.
I have an active Epstein-Barr virus infection.
I am getting chemoradiation for Stage III non-small cell lung cancer that can't be removed by surgery.
My lung cancer is a mix of small cell and non-small cell types.
I have or had lung conditions like fibrosis or pneumonia not caused by cancer treatment.
My Stage III NSCLC worsened despite platinum-based treatments.
I don't have lasting side effects worse than Grade 2 from previous treatments, except for hair loss.
I have lung inflammation from previous cancer treatments.
Treatment Details
The study compares the effectiveness and safety of Durvalumab combined with Domvanalimab versus Durvalumab with a placebo in patients who've had concurrent chemoradiation therapy for lung cancer. It's randomized, double-blind, and includes multiple international centers.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A: Durvalumab + DomvanalimabExperimental Treatment2 Interventions
Durvalumab and domvanalimab as an IV infusion q4w, starting on Day 1 for up to a maximum of 12 months
Group II: Arm B: Durvalumab + PlaceboActive Control2 Interventions
Durvalumab + placebo as an IV infusion q4w starting on Day 1 for up to a maximum of 12 months
Find a clinic near you
Research locations nearbySelect from list below to view details:
Research SiteLaval, Canada
Research SiteFountain Valley, CA
Research SiteBerkeley Heights, NJ
Research SiteFort Lauderdale, FL
More Trial Locations
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Who is running the clinical trial?
AstraZenecaLead Sponsor
Arcus Biosciences, Inc.Industry Sponsor
References
Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. [2022]PD-L1 and CTLA-4 immune checkpoints inhibit antitumour T-cell activity. Combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab might provide greater antitumour activity than either drug alone. We aimed to assess durvalumab plus tremelimumab in patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC).
Durvalumab: First Global Approval. [2022]Intravenous durvalumab (Imfinzi™; AstraZeneca) is a fully human monoclonal antibody that blocks programmed cell death ligand-1 binding to its receptors (PD-1 and CD80), resulting in enhanced T-cell responses against cancer cells. The US FDA has granted durvalumab accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Durvalumab ± tremelimumab is under phase III clinical trials in urothelial carcinoma, non-small cell lung cancer, small cell lung cancer and head and neck squamous cell carcinoma. The drug is also being evaluated in phase I or II clinical trials in a wide range of solid tumours and haematological malignancies. This article summarizes the milestones in the development of durvalumab leading to this first approval for urothelial carcinoma.
Durvalumab in non-small-cell lung cancer patients: current developments. [2018]Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population. Durvalumab is under evaluation in early, locally advanced and advanced disease as monotherapy and combined with ICIs, targeted therapies, chemotherapy and radiotherapy. Impressive activity has been recently reported after chemoradiation in locally advanced patients; promising activity was observed with other ICI combinations, and potentially with other drugs including platinum-based chemotherapy. In contrast, early data reveal lower response rates in EGFR and ALK-positive patients.
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]The prominent immune checkpoint molecule, programmed cell death ligand-1 (PD-L1), is the object of increasing attention. Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.
SWOG S1400A (NCT02154490): A Phase II Study of Durvalumab for Patients With Previously Treated Stage IV or Recurrent Squamous Cell Lung Cancer (Lung-MAP Sub-study). [2022]The objective of the Lung-MAP sub-study S1400A was to evaluate the response rate to durvalumab, an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with squamous non-small-cell lung cancer (SqNSCLC).
Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]Durvalumab is a programmed cell death ligand 1 (PD-L1) inhibitor indicated for stage III, unresectable non-small cell lung cancer (NSCLC) consolidation therapy following concurrent platinum-based chemoradiation based on results of the PACIFIC trial. Safety data of durvalumab demonstrates an increased risk of immune-related adverse effects (irAEs), most notably pneumonitis. Pneumonitis is a serious and potentially fatal complication of immunotherapy. It is important to investigate the incidence of pneumonitis in clinical practice to evaluate the generalizability of published data. The objective of this study is to assess and characterize real-world incidence of pneumonitis in patients with NSCLC receiving durvalumab.
Safety and Tolerability of MEDI0562, an OX40 Agonist mAb, in Combination with Durvalumab or Tremelimumab in Adult Patients with Advanced Solid Tumors. [2022]Combination therapies targeting immunologic checkpoints have shown promise in treating multiple tumor types. We report safety and tolerability of MEDI0562, a humanized IgG1K OX40 mAb, in combination with durvalumab (anti-PD-L1), or tremelimumab (anti-CTLA-4), in adult patients with previously treated advanced solid tumors.
Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab. [2022]Immune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4).
Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival.
Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). [2023]In the phase 3 POSEIDON study, first-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC). We present patient-reported outcomes (PROs).