Combination Therapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
+34 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Genentech, Inc.
Must not be taking: Chemotherapy, Immunotherapy, Radiotherapy, others
Disqualifiers: Prior lung cancer, HIV, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial will evaluate the efficacy and safety of various therapies in patients with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated non-small cell lung cancer (NSCLC) tumors that meet protocol-specified biomarker criteria
Will I have to stop taking my current medications?
The trial information does not specify if 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 combination therapy for lung cancer?
The combination of atezolizumab (an immune-checkpoint inhibitor) with stereotactic ablative radiotherapy (SABR) showed early responses in 17% of patients with early-stage non-small cell lung cancer, suggesting potential benefits. Additionally, the combination of a PD-L1 inhibitor with chemotherapy improved survival in small cell lung cancer, indicating that similar combinations might be effective in other lung cancer types.
12345Is the combination therapy for lung cancer generally safe in humans?
Alectinib, a drug used in combination therapy for lung cancer, is generally well tolerated but can cause serious side effects, including severe skin reactions and liver issues. It's important for patients to be closely monitored for these potential adverse effects.
678910What makes this lung cancer treatment unique?
This treatment is unique because it combines multiple therapies, including targeted drugs like Alectinib and Entrectinib, immunotherapy with Atezolizumab, and traditional chemotherapy, along with surgical and radiation options. This comprehensive approach aims to target different aspects of lung cancer, potentially improving outcomes compared to standard treatments that typically use fewer components.
15111213Eligibility Criteria
This trial is for adults with resectable, untreated Stage IB-III non-small cell lung cancer (NSCLC) that have specific biomarkers. They must be medically fit for surgery, have good organ function and performance status, and not have had any prior lung cancer treatments in the last 2 years. Participants should agree to use contraception and cannot join if they've had major surgery recently or other cancers within 3 years.Inclusion Criteria
You should not have hepatitis C virus (HCV) or it should not be active in your body.
I am fully active or can carry out light work.
My blood and organs are functioning well.
+14 more
Exclusion Criteria
Pregnant or lactating, or intending to become pregnant during the study
I haven't had lung cancer treatment in the last 2 years.
I haven't had any other cancers in the last 3 years, except for those with a low risk and curable outcome.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Neoadjuvant Treatment
Participants receive neoadjuvant treatment specific to their cohort (e.g., atezolizumab, pralsetinib, entrectinib, etc.) for up to 8 weeks before surgical resection
8 weeks
Surgical Resection
Participants undergo surgical resection per standard of care
1 week
Adjuvant Treatment
Participants receive adjuvant treatment specific to their cohort, including chemotherapy and/or targeted therapies for up to 2 years
Up to 2 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests multiple therapies including Divarasib, Vemurafenib, Alectinib, Chemotherapy, Resection (surgery), Cobimetinib, Pralsetinib, SBRT (a type of radiation therapy), Atezolizumab (immunotherapy), and Entrectinib on patients with NSCLC who meet certain genetic criteria. The goal is to see which treatment works best.
7Treatment groups
Experimental Treatment
Group I: ROS 1 CohortExperimental Treatment3 Interventions
Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib.
Group II: RET Cohort (Enrollment closed)Experimental Treatment3 Interventions
Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per standard of care. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with pralsetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of pralsetinib.
Enrollment closed.
Group III: PD-L1 CohortExperimental Treatment3 Interventions
Participants with positive PD-L1 in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, patients will also receive low-dose SBRT (8Gy X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per NCCN guidelines
Group IV: NTRK CohortExperimental Treatment3 Interventions
Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib.
Group V: KRAS G12C CohortExperimental Treatment2 Interventions
Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per standard of care. PD-L1 negative patients whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib for up to 2 years as adjuvant therapy. For patients who test positive PD-L1, they will have the option to receive Atezolizumab for up to 16 cycles.
Group VI: BRAF Cohort (Enrollment closed, no participants enrolled)Experimental Treatment4 Interventions
Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with vemurafenib plus cobimetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of of vemurafenib plus cobimetinib.
Enrollment closed.
Group VII: ALK CohortExperimental Treatment3 Interventions
Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with alectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of alectinib.
Alectinib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Alecensa for:
- Metastatic ALK-positive non-small cell lung cancer (NSCLC)
- Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC
🇪🇺 Approved in European Union as Alecensa for:
- Metastatic ALK-positive non-small cell lung cancer (NSCLC)
- Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Virginia Cancer SpecialistsFairfax, VA
Allegheny General HospitalPittsburgh, PA
Smilow Cancer CenterNorth Haven, CT
Baptist Clinical Research InstituteMemphis, TN
More Trial Locations
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Who Is Running the Clinical Trial?
Genentech, Inc.Lead Sponsor
Blueprint Medicines CorporationIndustry Sponsor
Chugai Pharmaceutical Co.Collaborator
Hoffmann-La RocheIndustry Sponsor
References
Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO). [2022]Non-small-cell lung cancer (NSCLC) causes significant mortality each year. After successful resection of disease stage IB (>4 cm) to IIIA (per AJCC 7), adjuvant platinum-based chemotherapy improves median overall survival and is the standard of care, but many patients still experience recurrence of disease. An adjuvant regimen with greater efficacy could substantially improve outcomes. Pembrolizumab, a programmed cell death-1 inhibitor, has become an important option in the treatment of metastatic NSCLC. ALCHEMIST is a clinical trial platform of the National Cancer Institute that includes biomarker analysis for resected NSCLC and supports therapeutic trials including A081801 (ACCIO), a three-arm study that will evaluate both concurrent chemotherapy plus pembrolizumab and sequential chemotherapy followed by pembrolizumab to standard of care adjuvant platinum-based chemotherapy. Clinical trial registration: NCT04267848 (ClinicalTrials.gov).
Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. [2022]Administration of pembrolizumab plus concurrent chemoradiation therapy (cCRT) may provide treatment benefit to patients with locally advanced, stage III non-small cell lung cancer (NSCLC).
ADC Shows Effectiveness in SCLC. [2015]Results from a phase I trial presented during the 2015 European Cancer Congress suggest that an experimental antibody-drug conjugate, rovalpituzumab tesirine, may be effective against recurrent small cell lung cancer, for which there are few treatment options.
Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes. We initiated a multi-institutional single-arm phase I study (NCT02599454) enrolling twenty patients with the primary endpoint of maximum tolerated dose (MTD); secondary endpoints of safety and efficacy; and exploratory mechanistic correlatives. Treatment is well tolerated and full dose atezolizumab (1200 mg) is the MTD. Efficacy signals include early responses (after 2 cycles of ICI, before initiation of SABR) in 17% of patients. Biomarkers of functional adaptive immunity, including T cell activation in the tumor and response to ex-vivo stimulation by circulating T cells, are highly predictive of benefit. These results require validation and are being tested in a phase III randomized trial.
Benmelstobart Ups ES-SCLC Survival. [2023]The combination of the PD-L1 inhibitor benmelstobart, the angiogenesis inhibitor anlotinib, and the chemotherapies etoposide and carboplatin significantly improved progression-free survival and overall survival compared with the chemotherapies alone in patients with newly diagnosed extensive-stage small cell lung cancer. Both survival measures were longer than those seen with any other trials in this population of patients.
Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. [2022]Alectinib is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring ALK rearrangements. Although generally well tolerated, alectinib can cause serious or life-threatening side effects.
Severe Skin Toxicity Caused by Sequential Anti-PD-1 Antibody and Alectinib in Non-small-cell Lung Cancer: A Report of Two Cases and a Literature Review. [2022]Immune checkpoint inhibitors (ICIs) have demonstrated marked efficacy in some cancer patients, but they may cause various severe immune-related adverse events. Alectinib is a second-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) approved for ALK-rearranged non-small-cell lung cancer (NSCLC). Alectinib is said to be safer than other TKIs. We conducted an investigator-initiated trial of alectinib, which also has RET kinase-inhibitory activity, against RET-rearranged NSCLC. Two RET-rearranged NSCLC patients experienced severe skin toxicity with alectinib after first undergoing anti-PD-1 antibody treatment with an ICI. These findings suggest that we should carefully follow patients for adverse effects of targeted drugs following ICI treatment.
Alectinib for advanced ALK-positive non-small-cell lung cancer. [2019]The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosage and administration, and place in therapy of alectinib for treatment of patients with non-small-cell lung cancer (NSCLC) are reviewed.
Safety Monitoring Activity During EGFR or Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients With Lung Cancer. [2023]Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are highly effective for treatment of EGFR- or ALK-mutated lung cancer. Nevertheless, they are associated with several unique toxicities. Although the available US Food and Drug Administration (FDA)-approved drug label can provide guidance for safety monitoring, its integration into clinical practice has not been previously described. We studied the conduct of safety monitoring activity (SMA) at a large academic institution. On the basis of FDA-approved drug labels, two drug-specific SMAs were identified for osimertinib, crizotinib, alectinib, or lorlatinib. Electronic medical records of patients initiated on these drugs from 2017 to 2021 were retrospectively reviewed. Each course of treatment was evaluated for the occurrence of SMAs and the corresponding adverse events. Analyses included 130 treatment courses from 111 unique patients. For each SMA evaluated, the prevalence of SMA conduct ranged from 10.0% to 84.6%. The most frequently conducted SMA was ECG for lorlatinib therapy and the least was creatine phosphokinase analysis for alectinib. We observed none of the assessed SMAs being conducted in 41 treatment courses (31.5%). EGFR inhibitor predicted a higher likelihood of both SMAs being conducted than ALK inhibitors (P = .02). Serious, grade 3 or 4 adverse events were observed in 21 treatment courses (16.2%), including one grade 4 transaminitis related to alectinib. On the basis of our experience, the conduct of SMA was more challenging to implement for ALK inhibitor than for EGFR inhibitor. Clinicians should be vigilant and review the FDA-approved drug label before prescribing.
Enteral administration of alectinib for ALK-positive non-small cell lung cancer in an elderly patient: A case report. [2023]Alectinib is a tyrosine kinase inhibitor (TKI) approved for use as first-line metastatic therapy for patients with anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Certain medical conditions related to the tumor lesions may not allow oral administration of TKIs.
Chemotherapy in metastatic non-small-cell lung cancer. [2022]Over the last decade, a group of new agents with differing mechanisms of action have shown great promise in early clinical studies in non-small-cell lung cancer (NSCLC). These include the taxanes docetaxel (Taxotere) and paclitaxel (Taxol); the nucleoside analog gemcitabine (Gemzar); the vinca alkaloid vinorelbine (Navelbine); the topoisomerase-I inhibitor irinotecan (Camptosar, CPT-11); and the bioreductive agent tirapazamine. Cisplatin (Platinol), which has been the "backbone" of combination chemotherapy in patients with NSCLC because of its proven single-agent activity, has been examined in combination with these agents as well as radiation and surgery in numerous trials. This article summarizes trials of these combination therapies in the treatment of NSCLC.
Triplet combination chemotherapy and targeted therapy regimens. [2005]Current agents for the treatment of non-small-cell lung cancer include gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), vinorelbine (Navelbine), and irinotecan (CPT-11, Camptosar). Experimental agents include pemetrexed (LY231514, Alimta) and tirapazamine. Molecular and biological therapies include angiogenesis inhibitors, epidermal growth factor receptor inhibitors, HER2/neu inhibitors, and inhibitors of ras activation and function. Doublet chemotherapy is currently the standard treatment for advanced non-small-cell lung cancer. In the past 2 years, randomized trials have shown that many of the new two-drug combinations used to treat non-small-cell lung cancer have equivalent efficacy. These combinations produce 1-year survival rates of about 35% and 2-year survival rates of about 15%. Toxicity rates vary but are sufficiently low as to make the development of three-drug combinations feasible. Preliminary studies from several phase I and II trials suggest that triplet therapy can improve survival beyond that of double therapy regimens.
Alterations in genes other than EGFR/ALK/ROS1 in non-small cell lung cancer: trials and treatment options. [2020]During the last decade, we have seen tremendous progress in the therapy of lung cancer. Discovery of actionable mutations in EGFR and translocations in ALK and ROS1 have identified subsets of patients with excellent tumor response to oral targeted agents with manageable side effects. In this review, we highlight treatment options including corresponding clinical trials for oncogenic alterations affecting the receptor tyrosine kinases MET, FGFR, NTRK, RET, HER2, HER3, and HER4 as well as components of the RAS-RAF-MEK signaling pathway.