There is great excitement around the potential benefits of adding immunotherapy to different treatment combinations for lung cancer. Biomarker testing is an important part of this approach because it can identify which patients can get the most benefit from targeted therapy. In fact, the 2018 NCCN Guidelines now recommend molecular testing as part of the initial diagnosis in patients with nonsmall cell lung cancer (NSCLC).
At City of Hope, we continue to pioneer treatment in lung cancer with studies that incorporate biomarker testing and immunotherapy to give patients the best care possible. Our ongoing clinical trials reflect the rapidly changing landscape of lung cancer therapy.
From checkpoint inhibitors to epidermal growth factor receptor (EGFR) antibody, tyrosine kinase inhibitors (TKIs), T cell engager, mTOR inhibitor, RET kinase inhibitors and more, the therapies being evaluated in our clinical trials cover a multitude of mechanisms of action to stay one step ahead of a constantly changing disease.
In all, the trials aim to provide novel therapeutic regimens in cases of NSCLC or small cell lung cancer (SCLC) where there are currently few or no treatment options. Below is an overview of ongoing clinical trials in lung cancer at City of Hope with links to the clinicaltrials.gov pages for each of the studies.
Phase II study in NSCLC (NCT02927301): A Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Resectable NSCLC—Lung Cancer Mutation Consortium 3
This study couples the efficacy of the PD-L1 checkpoint inhibitor atezolizumab with surgery in patients with resectable NSCLC who have had no prior therapy for lung cancer. If this treatment regimen proves successful, it could postpone the use of powerful but debilitating chemotherapy or radiation. Karen Reckamp, M.D., M.S., co-director of our Lung Cancer and Thoracic Oncology Program, will be leading this trial.
Phase II study in NSCLC (NCT03334617): Phase II Umbrella Study of Novel Anti-cancer Agents in Patients With NSCLC Who Progressed on an Anti-PD-1/PD-L1-Containing Therapy
This study, which is being done in collaboration with AstraZeneca and the MD Anderson Cancer Center, is an ambitious umbrella study that will test six different therapeutic agents in NSCLC that has progressed after the administration of immune checkpoint inhibitors and platinum-doublet therapies. Treatment arm assignment is guided by the identification of tumor-acquired genetic mutations because the efficacy of the different drugs being evaluated is mutation specific. This trial will be led by Marianna Koczywas, M.D.
Phase I study in NSCLC (NCT02592577): MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC
A phase I trial in patients with Stage IIIb or Stage IV NSCLC will evaluate the safety and efficacy of MAGE A10ᶜ⁷⁹⁶T cells, which are autologous T cells that have been genetically modified to destroy NSCLC tumors expressing the MAGE-A10 protein. This protein is frequently expressed by NSCLC tumor cells. Karen Reckamp, M.D., M.S., will be leading this trial at the main City of Hope campus in Duarte, California.
Phase I study in EGFR-mutant NSCLC (NCT02496663): Osimertinib and Necitumumab in Treating Patients With EGFR-Mutant Stage IV or Recurrent NSCLC Who Have Progressed on a Previous EGFR TKI
This study combines two drugs with different mechanisms of action — the EGFR antibody necitumumab and the TKI osimertinib — to provide a treatment option for patients with advanced EGFR-positive NSCLC who have progressed on a previous TKI. Biomarker identification is a key part of study protocol, which requires that patients have one of six different EGFR-activating mutations. The study’s principal investigator is Marianna Koczywas, M.D., medical oncologist at City of Hope and clinical professor in the Department of Medical Oncology & Therapeutics Research.
Phase I/II study in NSCLC (NCT03157128): Phase 1/2 Study of LOXO-292 in Patients With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer
This multiphase clinical trial is testing a new drug candidate in NSCLC, as well as other carcinomas. Developed by Loxo Oncology, LOXO-292 is a highly selective RET kinase inhibitor that could provide another targeted treatment option for patients with locally advanced or metastatic solid tumors in NSCLC. This trial will be led by Karen Reckamp, M.D., M.S.
Small Cell Lung Cancer
Phase I study in SCLC (NCT03319940): Study Evaluating Safety, Tolerability and PK of AMG 757 in Adults With SCLC
This study is evaluating a novel therapy to treat SCLC. Amgen’s new drug candidate, AMG 757, is known as a half-life extended, bispecific, T cell engager (BiTE) that targets delta-like protein 3 (DLL3), which is often mutated in SCLC. The principal investigator for this trial is Ravi Salgia, M.D., Ph.D., Arthur & Rosalie Kaplan Chair in Medical Oncology and chair of the Department of Medical Oncology & Therapeutics Research.