Durvalumab + Oleclumab/Monalizumab for Lung Cancer
(PACIFIC-9 Trial)
Recruiting in Palo Alto (17 mi)
+188 other locations
Overseen ByFabrice Barlesi, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must not be taking: Immunosuppressants
Disqualifiers: Other malignancy, Pneumonitis, Autoimmune disorders, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing two drug combinations to help the immune system fight advanced lung cancer that can't be surgically removed. The patients have already had previous treatment without their disease getting worse. The drugs aim to boost the immune response to better identify and kill cancer cells.
Will I have to stop taking my current medications?
The trial requires that you stop using immunosuppressive medications (drugs that lower the body's ability to fight infections) within 14 days before starting the study treatment. 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 Durvalumab, Oleclumab, and Monalizumab for lung cancer?
Research shows that combining Durvalumab with Oleclumab or Monalizumab improves the response rate in lung cancer patients compared to using Durvalumab alone. This combination leads to better immune system activation against tumors, which is promising for treating lung cancer.
12345What safety data exists for Durvalumab and related treatments in humans?
Durvalumab, also known as Imfinzi, has been studied for safety in various cancers. In the PACIFIC trial for lung cancer, about 25% of patients experienced immune-related side effects, with serious cases in 3.4% of patients. Other studies show that combining Durvalumab with another drug, Tremelimumab, increases the risk of serious side effects compared to using Durvalumab alone.
46789How is the drug combination of Durvalumab, Oleclumab, and Monalizumab unique for lung cancer?
This drug combination is unique because it builds on the standard treatment of durvalumab, an immune checkpoint inhibitor, by adding oleclumab and monalizumab, which target different immune pathways to potentially enhance the immune response against cancer cells in patients with stage III non-small cell lung cancer.
2341011Eligibility Criteria
Adults over 18 with Stage III unresectable Non-Small Cell Lung Cancer (NSCLC) who haven't worsened after platinum-based chemoradiation. They must have normal organ function, no history of certain autoimmune diseases or other cancers within the last 5 years, and not be on immunosuppressants.Inclusion Criteria
I have provided a tumor tissue sample before starting CRT.
My organs and bone marrow are working well.
Your tumor has been tested for PD-L1 status by a central laboratory.
+7 more
Exclusion Criteria
My lung cancer is a mix of small cell and non-small cell types.
My Stage III NSCLC has worsened despite platinum-based treatments.
I don't have lasting side effects from previous cancer treatments, except for hair loss.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Durvalumab in combination with Oleclumab or Monalizumab, or Durvalumab with placebo, administered in 28-day cycles for up to 12 months
12 months
Monthly visits for drug administration
Follow-up
Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival assessments
Up to 9 years
Participant Groups
The study is testing Durvalumab in combination with either Oleclumab or Monalizumab against a placebo to see if they improve outcomes for NSCLC patients post-chemoradiation. It's randomized and double-blind, meaning neither doctors nor patients know who gets which treatment.
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm B: Durvalumab and MonalizumabExperimental Treatment3 Interventions
Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only
Group II: Arm A: Durvalumab and OleclumabExperimental Treatment2 Interventions
Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
Group III: Arm C: Durvalumab and PlaceboActive Control2 Interventions
Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
Durvalumab is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Imfinzi for:
- Locally advanced, unresectable non-small cell lung cancer (NSCLC)
🇺🇸 Approved in United States as Imfinzi for:
- Extensive-stage small cell lung cancer (ES-SCLC)
- Limited-stage small cell lung cancer (LS-SCLC)
- Locally advanced or metastatic urothelial carcinoma
🇯🇵 Approved in Japan as Imfinzi for:
- Not specified in provided sources
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteIthaca, NY
Research SiteYork, PA
Research SiteBethesda, MD
Research SiteCleveland, OH
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
References
Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial. [2023]Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non-small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation.
COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer. [2022]Durvalumab significantly improves overall survival for patients with unresectable stage III non-small-cell lung cancer and no progression after concurrent chemoradiotherapy (cCRT). Building upon that standard of care, COAST is a phase II study of durvalumab alone or combined with the anti-CD73 monoclonal antibody oleclumab or anti-NKG2A monoclonal antibody monalizumab as consolidation therapy in this setting.
Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. [2020]Immune checkpoint inhibitors (ICIs) have transformed the therapeutic strategy and prognosis of advanced non-small cell lung cancer (NSCLC) patients. Nowadays, ICIs as monotherapy or in combination with chemotherapy are the standard of care treatment in advanced NSCLC, and in stage III, durvalumab (a programmed death ligand 1 inhibitor) is the unique drug approved as consolidation treatment after chemo-radiotherapy. This article reviews the pharmacological properties, clinical activity and safety of durvalumab as monotherapy or in combination with chemotherapy or other ICIs in the therapeutic strategy of NSCLC patients.
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.
Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [2022]Label="PURPOSE">The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non-small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.
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.
Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. [2022]Immune-mediated adverse events (imAEs), including all-cause immune-mediated pneumonitis, were reported in approximately 25% of patients in the placebo-controlled, phase III PACIFIC trial of durvalumab monotherapy (for up to 12 months) in patients with unresectable, stage III NSCLC and no disease progression after concurrent chemoradiotherapy; only 3.4% of patients experienced grade 3/4 imAEs. With broad application of the PACIFIC regimen (consolidation durvalumab after chemoradiotherapy), now standard-of-care in this setting, there is a need to better characterize the occurrence of imAEs with this regimen.
Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. Methods: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. Results: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p
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.
Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. [2022]Durvalumab is an anti-PD-L1 immune checkpoint inhibitor approved for consolidation therapy for patients with stage III non-small cell lung cancer (NSCLC) after chemoradiation. The purpose of our study was to evaluate the association between the degree of tumor PD-L1 expression and outcomes of stage III NSCLC patients treated with durvalumab.
MEDI 4736 (durvalumab) in non-small cell lung cancer. [2021]Immune checkpoint inhibitors (ICI) are now a therapeutic option for advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. Other notable PD-L1 inhibitors under development include avelumab and durvalumab. Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences. Ongoing clinical trials were also reviewed. Expert opinion: Early phase trials of durvalumab monotherapy (and in combination) have demonstrated activity in advanced NSCLC patients and it has demonstrated a good safety profile. The authors believe that durvalumab will likely play an important role in future treatment strategies for NSCLC. The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.