Re-Evaluating Eligibility Criteria for Oncology Clinical Trials: Analysis of Investigational New Drug Applications in 2015.

Clinical trial eligibility criteria are necessary to define the patient population under study and improve trial safety. However, there are concerns that eligibility criteria for cancer clinical trials are too restrictive and limit patient enrollment in clinical trials. Recently, there have been initiatives to re-examine and modernize eligibility criteria for oncology clinical trials.

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy.

Unlabelled: On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Multiple Myeloma.

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision-making about new drugs to treat multiple myeloma (MM). MM assessments have been based on endpoints such as time to progression (TTP), progression-free survival (PFS), and objective response rate (ORR) which are different than benefit-risk analysis based on overall survival (OS).

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond.

Unlabelled: On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co.

FDA Approval Summary: Trabectedin for Unresectable or Metastatic Liposarcoma or Leiomyosarcoma Following an Anthracycline-Containing Regimen.

On October 23, 2015, the FDA approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-patient, multicenter study comparing the safety and efficacy of trabectedin 1.5 mg/m as a 24-hour continuous intravenous (i.

FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious Mutation-Associated Advanced Ovarian Cancer.

On December 19, 2016, the FDA granted accelerated approval to rucaparib (RUBRACA; Clovis Oncology, Inc.) for the treatment of patients with deleterious mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies. The FDA also approved the FoundationFocus CDx test (Foundation Medicine, Inc.

U.S. Food and Drug Administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia.

The U.S. Food and Drug Administration (FDA) approved eltrombopag for pediatric patients with chronic immune (idiopathic) thrombocytopenia (ITP) ages ≥6 on June 11, 2015, and ages ≥1 on August 24, 2015.

Milestone Analyses of Immune Checkpoint Inhibitors, Targeted Therapy, and Conventional Therapy in Metastatic Non-Small Cell Lung Cancer Trials: A Meta-analysis.

Importance: Novel intermediate end points may be useful to detect signals of early activity and prioritize new therapies to treat patients with advanced malignant neoplasms, including metastatic non-small cell lung cancer (mNSCLC).

Objective: To explore milestone rate, a proposed intermediate end point for immunotherapy trials.

Data Sources: Trials submitted to the US Food and Drug Administration with more than 150 patients and in which the intention-to-treat population was assessed were identified.

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer.

On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR).

Oncology Drug Approvals: Evaluating Endpoints and Evidence in an Era of Breakthrough Therapies.

With the Breakthrough Therapy Designation program adding to the tools that the U.S. Food and Drug Administration (FDA) has for expediting drug development, the FDA reassessed the endpoints needed for approval of transformative therapies.

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy.

Unlabelled: On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp.

Regulatory considerations on endpoints in ovarian cancer drug development.

Ovarian cancer remains a disease entity that is responsible for considerable morbidity and mortality among women worldwide. Modern drug research pipelines and accelerated drug development timelines applied to other disease entities have begun to make an impact on treatment options for patients with advanced ovarian cancer, as exemplified by the recent accelerated approval of 2 agents for this disease as the forerunners of a growing number of registrational trials. Regulatory flexibility for this serious and life-threatening condition spurs the consideration of intermediate endpoints for regulatory trial design, including potential applications in the development of newer therapeutic classes such as targeted therapies and immunotherapies for patients with advanced ovarian cancer.

FDA Approval Summary: Nivolumab for the Treatment of Relapsed or Progressive Classical Hodgkin Lymphoma.

On May 17, 2016, after an expedited priority review, the U.S. Food and Drug Administration granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (BV).

FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy.

Unlabelled: Until recently in the United States, no products were approved for second-line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S.

Characterization of outcomes in patients with metastatic non-small cell lung cancer treated with programmed cell death protein 1 inhibitors past RECIST version 1.1-defined disease progression in clinical trials.

Based on anecdotal cases of clinically important decreases in tumor size following initial evidence of disease progression when treating patients with anti-PD-1 therapies, investigators have conducted clinical trials in patients with metastatic non-small lung cancer (mNSCLC) receiving anti-PD-1 therapy allowing for treatment past RECIST-defined disease progression (TPP). We describe the findings of a pooled analysis of three clinical trials submitted to the US Food and Drug administration (FDA) where treatment of patients with mNSCLC permitted TPP in terms of reduction in the sum of target lesions following initial RECIST-defined progression. We identified patients who received TPP and the characteristics and post-TPP change in tumor burden.

FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma.

On November 30, 2015, the FDA approved elotuzumab (Empliciti; Bristol-Myers Squibb) in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who received one to three prior therapies. FDA approval was based primarily on the results of a phase III, randomized, open-label, multicenter trial, CA204004, which evaluated elotuzumab in combination with lenalidomide and dexamethasone (E-Ld) compared with lenalidomide and dexamethasone (Ld) alone in patients with relapsed or refractory multiple myeloma. Coprimary endpoints were progression-free survival (PFS) and overall response rate (ORR).

FDA Approval Summary: Eribulin for Patients with Unresectable or Metastatic Liposarcoma Who Have Received a Prior Anthracycline-Containing Regimen.

On January 28, 2016, the FDA approved eribulin (Halaven; Eisai Inc.) for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen. The approval was based on results from a single, randomized, open-label, active-controlled trial (Trial E7389-G000-309) enrolling 452 patients with advanced, locally recurrent or metastatic liposarcoma or leiomyosarcoma.

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma.

On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial.