Targeted Drug Therapy for Non-Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+32 other locations
Overseen bySarah B Goldberg
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: SWOG Cancer Research Network
Must be taking: Osimertinib
Must not be taking: Anti-VEGF, MET inhibitors
Disqualifiers: Uncontrolled hypertension, Recent surgery, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This phase II Lung-MAP treatment trial test the combination of targeted drugs (capmatinib, osimertinib, and/or ramucirumab) in treating patients with non-small cell lung cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that has EGFR and MET gene changes. Capmatinib and osimertinib are in a class of medications called kinase inhibitors. They work by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells and may help shrink tumors. Ramucirumab is a monoclonal antibody that may prevent the growth of new blood vessels that tumors need to grow. Giving capmatinib, osimertinib, and/or ramucirumab and targeting abnormal gene changes in tumor cells may be effective in shrinking or stabilizing advanced non-small cell lung cancer.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop all current medications, but you cannot take certain drugs like strong inducers of CYP3A4, CYP3A4 inhibitors, and others that affect specific enzymes or prolong the QT interval. Osimertinib can be continued up to the day before starting the trial treatment.
What data supports the effectiveness of the drug osimertinib for treating non-small cell lung cancer?
Osimertinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with a specific mutation (EGFR T790M) that often develops resistance to earlier treatments. In clinical trials, it achieved significant tumor response rates, with 57% and 61% of patients showing improvement in two separate studies.12345
What makes the drug combination of Capmatinib and Osimertinib unique for treating non-small cell lung cancer?
This drug combination is unique because it targets specific genetic mutations in non-small cell lung cancer: Osimertinib targets the EGFR T790M mutation, which is common in patients who have developed resistance to previous treatments, while Capmatinib targets the MET exon 14 skipping mutation, providing a tailored approach for patients with these specific genetic profiles.12678
Eligibility Criteria
This trial is for adults with advanced non-small cell lung cancer that has spread and contains specific gene changes (EGFR and MET). Participants must have progressed on osimertinib treatment, be able to swallow pills, have adequate organ function, not be pregnant or breastfeeding, agree to use contraception if of reproductive potential, and not have certain medical conditions or treatments that could interfere with the study.Inclusion Criteria
I have recovered from previous treatment side effects, except for hair loss or skin color loss.
Your hemoglobin level is lower than 9.0 grams per deciliter within the last 28 days before the study starts.
Your platelet count is at least 100,000 per microliter of blood within the last 28 days before the study starts.
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Exclusion Criteria
I have not had a live vaccine in the last 28 days.
Participants must not be pregnant or breastfeeding (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of 'reproductive potential.' In addition to routine contraceptive methods, 'effective contraception' also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
I haven't taken any cancer drugs (except osimertinib) in the last 21 days.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive capmatinib, osimertinib, and optionally ramucirumab, with regular CT or MRI scans and blood sample collections
Up to 3 years
Regular visits for drug administration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment
4-8 weeks
Treatment Details
Interventions
- Capmatinib (Kinase Inhibitor)
- Osimertinib (Kinase Inhibitor)
- Ramucirumab (Monoclonal Antibody)
Trial OverviewThe trial tests a combination of targeted drugs: capmatinib (a kinase inhibitor), osimertinib (another kinase inhibitor), and ramucirumab (a monoclonal antibody). These drugs aim to block proteins signaling cancer cells to multiply and prevent tumor growth by stopping new blood vessels from forming. The effectiveness in shrinking or stabilizing lung cancer will be studied.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm B (capmatinib, osimertinib)Experimental Treatment5 Interventions
Patients receive capmatinib PO and osimertinib PO on study. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.
Group II: Arm A (capmatinib, osimertinib, ramucirumab)Experimental Treatment6 Interventions
Patients receive capmatinib PO, osimertinib PO, and ramucirumab IV on study. Patients also undergo CT scan or MRI and collection of blood samples throughout the trial.
Capmatinib is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Tabrecta for:
- Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping
🇪🇺 Approved in European Union as Tabrecta for:
- Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping
🇨🇦 Approved in Canada as Tabrecta for:
- Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Illinois CancerCare-PeoriaPeoria, IL
Illinois CancerCare - WashingtonWashington, IL
Northeast Georgia Medical Center-GainesvilleGainesville, GA
Memorial Medical CenterModesto, CA
More Trial Locations
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Who Is Running the Clinical Trial?
SWOG Cancer Research NetworkLead Sponsor
Southwest Oncology GroupLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]In 2015, the FDA approved an unprecedented number of new therapies for non-small cell lung cancer (NSCLC), among them therapies addressing specific genomic tumor subsets in the setting of development of resistance to first-line targeted therapy. Osimertinib (Tagrisso, formerly AZD9291; AstraZeneca) is indicated for patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy. It received breakthrough therapy designation, priority review status, and accelerated approval from the FDA. Clin Cancer Res; 23(3); 618-22. ©2016 AACR.
Osimertinib: First Global Approval. [2022]Osimertinib (Tagrisso(™), AZD9291) is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that is being developed by AstraZeneca for the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib has been designed to target the EGFR T790M mutation that is often present in NSCLC patients with acquired EGFR TKI resistance, while sparing wild-type EGFR. In November 2015, the tablet formulation of osimertinib was granted accelerated approval in the USA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC (as detected by an FDA-approved test) who have progressed on or after EGFR TKI therapy. Osimertinib has also been granted accelerated assessment status for this indication in the EU, and is in phase III development for first- and second-line and adjuvant treatment of advanced EGFR mutation-positive NSCLC in several countries. Phase I trials in patients with advanced solid tumours are also being conducted. This article summarizes the milestones in the development of osimertinib leading to this first approval for NSCLC.
Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]Osimertinib is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated efficacy in the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC) in prospective clinical trials.
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension; n = 201) and a fixed-dose, activity-estimating trial (AURA2; n = 210). Osimertinib was administered at 80 mg orally once daily. The objective response rates (ORR) per blinded independent committee review were 57% [95% confidence interval (CI), 50-64) in AURA extension and 61% (95% CI, 54-68) in AURA2. Median duration of response (DOR) could not be estimated. Supportive efficacy data from 63 patients in the dose-finding part of the FIH trial demonstrated an ORR of 51% (95% CI, 38-64), with a median DOR of 12.4 months. Common adverse events (AE) evaluated in 411 patients included diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Grade 3 to 4 AEs occurred in 28% of patients, and 5.6% discontinued treatment due to AEs. Clin Cancer Res; 23(9); 2131-5. ©2016 AACR.
Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. [2022]Osimertinib is effective in non-small-cell lung cancer (NSCLC) with an acquired epidermal growth factor receptor (EGFR) T790M mutation, the most common resistance mechanism to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs).
Capmatinib: First Approval. [2021]Capmatinib (Tabrecta™) is an oral, small molecule mesenchymal-epithelial transition (MET) inhibitor being developed by Novartis Oncology, under a license from Incyte Corporation, for the treatment of lung cancer. Capmatinib targets and selectively binds to MET, including the mutant variant produced by exon 14 skipping, and inhibits cancer cell growth driven by the mutant MET variant. In May 2020, oral capmatinib received its first global approval in the USA for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have a mutation that leads to MET exon 14 skipping, as detected by an FDA-approved test. Clinical development for the treatment of glioblastoma, liver cancer, malignant melanoma, breast cancer, colorectal cancer, head and neck cancer and solid tumours is ongoing in several countries. This article summarizes the milestones in the development of capmatinib leading to its first approval.
Osimertinib making a breakthrough in lung cancer targeted therapy. [2020]Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the evidence-based first-line treatment for advanced non-small-cell lung cancer that harbors sensitizing EGFR mutations (EGFRm(+)) such as exon 19 deletions and L858R substitutions in exon 21. However, acquired resistance to EGFR TKIs is mostly driven by a second-site EGFR T790M mutation, which negates their inhibitory activity. Osimertinib (AZD9291, Tagrisso™), an oral, third-generation EGFR TKI, has been designed to target the EGFR T790M mutation, while sparing wild-type EGFR. In this up-to-date review, focus is not only on the structure, mechanisms, and pharmacokinetics of osimertinib but also on summarizing clinical trials and making recommendations of osimertinib for patients with non-small-cell lung cancer.
Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]Osimertinib (TAGRISSO®) is an orally administered, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is approved for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFR sensitizing mutation (exon 19 deletion or exon 21 [L858R] substitution)-positive non-small cell lung cancer (NSCLC). In the pivotal ADAURA trial in adults with completely resected, early-stage, EGFR mutation-positive (EGFRm+) NSCLC, osimertinib adjuvant therapy significantly prolonged disease-free survival (DFS) compared with placebo in the overall population of patients with stage IB-IIIA disease, as well as in the primary population of patients with stage II-IIIA disease. A DFS benefit of osimertinib was seen irrespective of whether or not patients received prior adjuvant chemotherapy. Overall survival (OS) data were very immature at the time of the analysis of DFS, and more mature OS data are awaited with interest. Osimertinib adjuvant therapy did not adversely affect health-related quality of life and was generally well tolerated, with a manageable safety profile and no new safety signals identified. Based on the available evidence, osimertinib is thus an appropriate targeted option for the adjuvant treatment of adults with completely resected, stage IB-IIIA, EGFRm+ NSCLC.