NCI Corner - Interview with Shakun Malik, MD

NCI Corner - Interview with Shakun Malik, MD

Regulatory Agency Perspective
Apr 01, 2016
By Erik J. Mac Laren, PhD

In late 2015, the US National Cancer Institute (NCI) Thoracic Malignancy Steering Committee (TMSC) published its strategic priorities for the coming years. These include: (1) innovative clinical trials to facilitate the development of immunotherapies and targeted therapies; (2) rapid testing of new agents to treat small cell lung cancer (SCLC); (3) exploration of neoadjuvant therapy for resectable non-small cell lung cancer (NSCLC); and (4) determining the optimal roles for new radiation approaches such as stereotactic body radiation therapy (SBRT).1 IASLC Lung Cancer News spoke with Shakun Malik, MD, Head, Thoracic and Head & Neck Cancer Therapeutics, from the NCI Cancer Therapy Evaluation Program (CTEP), and a member of the TMSC, about these goals and the future of thoracic cancer trials under the aegis of the NCI.

Q: What is your current vision for the NCI Thoracic Oncology Program?

A: My vision is to enhance our preclinical and translational work in a way that ultimately helps us design clinical trials leading to new innovative treatments to improve the care and overall survival of patients with lung cancer. There are many molecular targets that have been discovered recently; however, we need to get a better understanding of how they drive tumor growth. We now have a proliferation of immunotherapies in oncology, but we still do not know which patients will benefit the most from these new agents. In clinical trials data, there is a tail end of the curve where some patients have benefited the most. We need to focus our efforts and learn more about the tumor characteristics of these patients.

With the focus on expanding Precision Medicine clinical trials, there is an opportunity for all of us (NCI, pharma industry, FDA, and private sectors) to work in unison to accelerate clinical research leading towards improvements in treatment.

Q: How do you see the NCI functioning in the context of both industry and the National Clinical Trials Network (NCTN), which was formerly known as the Cooperative Group Program?

A: I do not think that one can function without the other in this era of precision medicine clinical trials and drug development. There has to be cooperation among all stakeholders, particularly industry, the NCTN, the NCI, and the FDA. With the discovery of multiple molecular targets that drive cancer cell growth, a common cancer like lung cancer is now recognized as having multiple molecular subtypes of the disease. Collaborations among all stakeholders can accelerate progress on new treatments.

Q: Please describe the concept behind master protocols like S1400. Where else in thoracic oncology do you think this can be implemented?

A: The concept of using master protocols came about in 2012, during an NCI and FDA workshop that led to the development of the Lung-MAP and ALCHEMIST trials.2 The goal was to provide a centralized screening approach in one master protocol in order to match patients to sub-studies testing investigational new treatments based on the molecular characterization of their tumors instead of mounting multiple, separate clinical trials. It takes an extensive infrastructure and resources to conduct master protocols. Of course, there has been a bit of a learning process with these new master protocol studies, but I think both of the trials are doing very well. This strategy can be implemented in other areas as well when there is a need for a centralized screening approach to match patients to studies based on the molecular characteristics of their tumors.

Q: Can you tell us what studies have been approved by CTEP recently?

A: There are a number of studies that we are working on currently. Over the last year, we have added a combination immunotherapy arm to Lung-MAP for patients with advanced squamous cell lung cancer in the second-line clinical setting. For ALCHEMIST, we have approved an additional treatment trial that will test an immunotherapeutic agent, nivolumab, in patients with resected early-stage lung cancer after completion of standard therapy. In addition to activating a study of afatinib, (a second-generation EGFR small molecule inhibitor) with or without cetuximab (an EGFR antibody) in patients with EGFR mutation in their tumors, a trial of immunotherapy with or without Stereotactic Body Radiation Therapy (SBRT) in limited metastatic setting has also just been approved. Several phase I and small phase II trials testing other new investigational treatments have also been approved by CTEP’s early-phase Experimental Therapeutics Clinical Trials Network (ETCTN).

Q: What other issues should be addressed by the NCI and the NCTN?

A: The NCTN is intended to encourage a consistently excellent clinical trials program executed by an integrated Network of Groups conducting trials across a broad range of diseases and diverse patient populations. The challenge is to continue to work together to design and conduct clinically meaningful trials and to use the resources of the entire network to ensure timely completion of the studies in order to accelerate progress in cancer treatment.

1. Thoracic Malignancy Steering Committee. 2015 Strategic Priorities: Thoracic Malignancy Steering Committee (TMSC). National Cancer Institute; November 2015.

2. Malik SM, Pazdur R, Abrams JS, et al. Consensus report of a joint NCI thoracic malignancies steering committee: FDA workshop on strategies for integrating biomarkers into clinical development of new therapies for lung cancer leading to the inception of “master protocols” in lung cancer. J Thorac Oncol. 2014;9(10):1443-1448.