Sotorasib vs Durvalumab for Lung Cancer
Recruiting in Palo Alto (17 mi)
+11 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must be taking: Durvalumab
Disqualifiers: Pregnancy, Active malignancy, Prior pneumonitis, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?In this study, the researchers will look at whether having participants switch from durvalumab to sotorasib when they have detectable minimal residual disease (MRD) is an effective treatment approach for locally advanced non-small cell lung cancer (LA-NSCLC). The researchers will see whether this switch to sotorasib can control LANSCLC longer compared to the treatment approach of staying on durvalumab (and not switching to sotorasib).
Do I need to stop my current medications for the trial?
The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants will switch from durvalumab to sotorasib if they have detectable minimal residual disease. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Durvalumab for lung cancer?
Durvalumab has shown effectiveness in treating non-small cell lung cancer (NSCLC), especially in patients with high PD-L1 expression, and is approved for use after chemoradiation in locally advanced cases. It has demonstrated improved disease control and survival in these patients.
12345Is Durvalumab safe for use in humans?
Durvalumab, used alone or with other drugs, has shown a manageable safety profile in treating advanced non-small cell lung cancer and other solid tumors. However, combining it with tremelimumab may increase the risk of side effects like reduced appetite and diarrhea.
12678How is the drug Sotorasib vs Durvalumab unique for lung cancer treatment?
Durvalumab is unique because it is an immune checkpoint inhibitor that blocks PD-L1, helping the immune system attack cancer cells, and is specifically approved as a consolidation treatment after chemoradiotherapy for stage III non-small cell lung cancer. Sotorasib, on the other hand, targets a specific mutation in the KRAS gene, which is a common mutation in lung cancer, offering a targeted approach for patients with this genetic profile.
12459Eligibility Criteria
This trial is for people with a type of lung cancer called locally advanced non-small cell lung cancer (LA-NSCLC). Participants should have minimal residual disease (MRD) detectable after initial treatment. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.Inclusion Criteria
My liver tests are within normal limits.
I am 18 years old or older.
No evidence of radiographic progression as measured through SOC imaging
+18 more
Exclusion Criteria
Prior pneumonitis
Pregnant or lactating women
I haven't had any other cancer except for certain types in the last year.
+2 more
Trial Timeline
Pre-Monitoring
Patients with LANSCLC with a KRAS G12C mutation undergo chemoradiation and clinical assessments per standard of care.
Varies
Monitoring
Patients with detectable ctDNA post-chemoradiation start durvalumab consolidation and have ctDNA measured again early-on during durvalumab consolidation.
Approximately 6 weeks
Randomization
Patients are randomized to continue durvalumab or switch to sotorasib, with a 28-day washout period for those switching to sotorasib.
Up to 12 months for durvalumab, until progression for sotorasib
Follow-up
Participants are monitored for safety and effectiveness after treatment, with progression-free survival as a primary endpoint.
Up to 3 years
Participant Groups
The study tests if switching from durvalumab to sotorasib when MRD is detected can better control LA-NSCLC compared to staying on durvalumab alone. It's about finding the most effective treatment timing and combination for this condition.
2Treatment groups
Experimental Treatment
Active Control
Group I: switch sotorasib treatment until progressionExperimental Treatment1 Intervention
Will receive sotorasib at 960 mg daily until progression. A dose de-escalation regimen based on toxicity will be implemented as below. If 120 mg cannot be tolerated, sotorasib will be discontinued and the patient will be removed from the trial.
Group II: continue standard of care (SOC) durvalumab treatmentActive Control1 Intervention
Will continue to receive durvalumab, 10 mg/kg IV every 2 weeks or 1500 mg/kg IV every 4 weeks 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:
University of Michigan (Data Collection Only)Ann Arbor, MI
Vanderbilt University (Data Collection Only)Nashville, TN
University of Miami (Data Collection Only)Miami, FL
Lehigh Valley Health Network (Dara Collection Only)Allentown, PA
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
AmgenIndustry Sponsor
References
Durvalumab for the treatment of non-small cell lung cancer. [2019]In non-small cell lung cancer (NSCLC), immunotherapy is one of today's most important and ground-breaking systemic treatments, mainly represented by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death protein 1 or ligand 1 (PD-1/PD-L1). Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2. Areas covered: In advanced NSCLC patients, durvalumab has demonstrated activity and acceptable tolerability, particularly with ≥25% PD-L1 tumor expression in the EGFR and ALK wild-type population. However, preliminary data have shown lower efficacy in EGFR mutant and ALK-positive patients. The results from the recent PACIFIC study in locally advanced patients have placed durvalumab as standard of care in consolidation after chemoradiation, leading to Food and Drug Administration (FDA) approval. Expert commentary: Early data suggest promising activity for durvalumab with the CTLA-4 inhibitor tremelimumab, regardless of PD-L1 expression, and potentially in combination with other drugs such as platinum-doublet chemotherapy. However, treatment-related toxicity associated with the combinations is an important aspect of the benefit-risk evaluation in the decision-making process. Results of ongoing phase III trials will provide illuminating data to confirm the place of durvalumab in the management of NSCLC patients.
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.
Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. [2023]The addition of consolidative durvalumab to chemoradiation has improved disease control and survival in locally advanced non-small cell lung cancer (NSCLC). However, there remains a need to identify biomarkers for response to this therapy to allow for risk adaptation and personalization.
Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration. [2023]Real-world evidence is limited regarding the relationship between race and use of durvalumab, an immunotherapy approved for use in adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This study aimed to evaluate if durvalumab treatment patterns differed by race in patients with unresectable stage III NSCLC in a Veterans Health Administration (VHA) population.
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 for the treatment of non-small cell lung cancer. [2020]Introduction: The prognosis of patients with advanced non-small cell lung cancer (NSCLC) remains poor, with a 5-year overall survival rate of around 15%. Immune checkpoint inhibitors, such as programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) inhibitors, have opened a new era in the management of NSCLC. Three checkpoint inhibitors (nivolumab, pembrolizumab, and atezolizumab) are currently approved by the US Food and Drug Administration (FDA) for advanced NSCLC. Durvalumab, an anti-PD-L1 antibody, is under investigation in several trials.Areas covered: This article reviews the pharmacological properties, clinical efficacy, and safety of durvalumab as monotherapy and in combination with other drugs for the treatment of locally advanced and advanced NSCLC.Expert opinion: Durvalumab as monotherapy or in combination with tremelimumab was effective with well-tolerated safety profiles for advanced NSCLC in several phase I or II studies. The PACIFIC study assessed the effectiveness of durvalumab as maintenance therapy following definitive chemoradiotherapy for unresectable stage III NSCLC, and met its primary endpoints of progression-free survival and overall survival. These results led to FDA approval for this NSCLC population. It will be exciting to follow ongoing phase III studies assessing how durvalumab fits into the rapidly evolving therapeutic landscape for advanced NSCLC.
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.
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
Early administration of durvalumab after chemoradiotherapy increased risk of pneumonitis in patients with locally advanced non-small cell lung cancer. [2023]Durvalumab (Durva) administration after chemoradiation therapy (CRT) in locally advanced non-small-cell lung cancer (NSCLC) is the standard of care, associated with relatively prolonged progression-free (PFS) and overall survival. However, pneumonitis occurs in 73.6% of Japanese patients. This retrospective study aimed to identify factors associated with Durva efficacy and safety, specifically, the risk of pneumonitis.