Divarasib + Pembrolizumab for Non-Small Cell Lung Cancer
(Krascendo 170 Trial)
Recruiting in Palo Alto (17 mi)
+85 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Hoffmann-La Roche
Must not be taking: KRAS inhibitors
Disqualifiers: Squamous NSCLC, CNS metastases, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called divarasib along with other cancer treatments. It focuses on people with advanced or metastatic non-small cell lung cancer. The study aims to see how divarasib moves through the body, its safety, and if it helps fight the cancer.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the drug pembrolizumab for non-small cell lung cancer?
Pembrolizumab has been shown to improve survival in patients with advanced non-small cell lung cancer, as it was approved by the FDA based on studies demonstrating significant improvements in survival compared to chemotherapy.
12345Is the combination of Divarasib and Pembrolizumab safe for humans?
Pembrolizumab, one of the drugs in the combination, has been used in treating non-small cell lung cancer and is generally considered safe, but it can cause some immune-related side effects, like type 1 diabetes in rare cases. There is no specific safety data available for Divarasib in the provided research.
12567What makes the drug combination of Divarasib and Pembrolizumab unique for treating non-small cell lung cancer?
The combination of Divarasib (GDC-6036) and Pembrolizumab is unique because it combines a novel investigational drug with an established immune checkpoint inhibitor, potentially enhancing the immune system's ability to fight non-small cell lung cancer by targeting different pathways.
12389Eligibility Criteria
This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that hasn't been treated yet and has a specific mutation called KRAS G12C. Participants need to have measurable disease, be in good physical condition (ECOG 0 or 1), and provide tumor tissue samples. They can't join if they've had another cancer within the last 5 years, untreated brain metastases, uncontrolled symptoms from their cancer, prior treatment with KRAS G12C inhibitors, certain lung conditions, active infections like TB, or recent heart problems.Inclusion Criteria
My condition has the required biomarker.
I am fully active or can carry out light work.
I can provide a sample of my tumor in the required format for the study.
+3 more
Exclusion Criteria
Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)
I have not had serious lung or heart issues in the last 3 months.
My lung cancer is of the squamous cell type.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive divarasib in combination with pembrolizumab and potentially chemotherapy, with dose finding and expansion stages
Up to approximately 3 years
Every 3 weeks (in-person for IV infusions)
Follow-up
Participants are monitored for safety, pharmacokinetics, and activity after treatment
Up to approximately 3 years
Participant Groups
The study tests Divarasib combined with other anti-cancer drugs: Pemetrexed, Cisplatin/Carboplatin and Pembrolizumab in patients who haven’t received any previous treatments for their NSCLC. It aims to assess how safe this combination is and how it affects the body (pharmacokinetics) as well as its effectiveness against the cancer.
2Treatment groups
Experimental Treatment
Group I: Cohort B - Combination Dose Finding + Dose ExpansionExperimental Treatment5 Interventions
Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) QD combined with pembrolizumab 200 mg IV Q3W plus investigator's choice of platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed.
Group II: Cohort A - Combination Dose Finding + Dose ExpansionExperimental Treatment2 Interventions
Participants enrolled in this cohort will receive divarasib (different dose levels will be evaluated) once a day (QD) combined with pembrolizumab 200 mg intravenous (IV) infusion every 3 weeks (Q3W).
During the expansion stage, some participants are planned to be randomized to one divarasib combination dose level; other participants are planned to be randomized to another divarasib combination dose level. Divarasib will be given in combination with pembrolizumab.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MD Anderson Cancer Center; OncologyHouston, TX
UCSD Moores Cancer CenterLa Jolla, CA
NYU Cancer Center; NYU Cancer InstituteNew York, NY
Yale Cancer CenterNew Haven, CT
More Trial Locations
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Who Is Running the Clinical Trial?
Hoffmann-La RocheLead Sponsor
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. [2022]In the phase I KEYNOTE-001 study, pembrolizumab demonstrated durable antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC). We sought to characterize the relationship between pembrolizumab dose, exposure, and response to define an effective dose for these patients.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]Pembrolizumab (Keytruda; Merck Sharp & Dohme) is a humanized IgG4 monoclonal antibody used in cancer immunotherapy. It targets the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, immune checkpoint blockade is associated with a risk for immune-related adverse events (irAEs) potentially affecting the endocrine organs. Type 1 diabetes mellitus is a rare irAE of PD-1 inhibitors, occurring in 0.2% of cases.
First-line pembrolizumab for non-small cell lung cancer patients with PD-L1 ≥50% in a multicenter real-life cohort: The PEMBREIZH study. [2021]The KEYNOTE-024 trial demonstrated that pembrolizumab, a PD-1 inhibitor, significantly improves progression-free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real-life conditions.
Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.
Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]Pembrolizumab is a highly selective IgG4 kappa isotype monoclonal antibody against the programmed cell death-1 (PD-1) molecule. In the treatment of non-small cell lung cancer (NSCLC), pembrolizumab has demonstrated significant efficacy, significant survival outcomes, long-lasting responses, and a good safety profile compared with cytotoxic chemotherapy.