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A number of large pharmaceutical companies have forged clinical trial collaborations focused on the investigation of novel combinations and companion diagnostics across multiple cancer indications.
A number of large pharmaceutical companies have forged clinical trial collaborations focused on the investigation of novel combinations and companion diagnostics across multiple cancer indications, according to several statements released in the past month.
Many of these partnerships look to capitalize on the growing field of immunotherapy, through novel drug combinations with PD-1 inhibitors. Additionally, as more genomic information becomes available, companies are looking toward agreements to meet the ever-growing need for biomarkers and molecular assays.On August 20, Bristol-Myers Squibb (BMS) and Celgene announced plans to establish a phase I clinical trial program focused on the combination of the PD-1 inhibitor nivolumab and nab-paclitaxel (Abraxane) across multiple tumors types. The study is expected to begin enrolling patients toward the end of 2014 for patients with HER2-negative breast cancer, non-small cell lung cancer (NSCLC), and pancreatic cancer.
The FDA initially approved nab-paclitaxel in 2005 as a treatment for patients with metastatic breast cancer following progression on combination chemotherapy. In 2012, the FDA approved the drug as a frontline treatment for patients with advanced NSCLC in combination with carboplatin. In 2013, nab-paclitaxel plus gemcitabine was approved as first-line treatment for patients with metastatic pancreatic cancer.
Following the approved indications for nab-paclitaxel, patients in the NSCLC arm of the phase I study will also receive carboplatin with nab-paclitaxel and nivolumab. Additionally, patients with pancreatic cancer will receive gemcitabine, nab-paclitaxel, and nivolumab.
Nivolumab made an impressive first appearance at the 2012 ASCO Annual Meeting, when it turned heads as a single-agent treatment for patients with melanoma, NSCLC, and renal cell carcinoma (RCC). In early 2014, BMS announced plans for a rolling submission for nivolumab as a third-line treatment for patients with squamous cell NSCLC. Additionally, the submission of a New Drug Application for nivolumab as a treatment for patients with melanoma is anticipated in the coming months.
“We believe that Abraxane is appropriate as a combination partner for novel immuno-oncology therapies due to its proven anti-tumor activity and that it can be administered without steroid premedication,” Markus Renschler, MD, senior vice president and global head of Hematology & Oncology Medical Affairs at Celgene, said in a release. “Our collaboration with Bristol-Myers Squibb further underscores our commitment to understanding and modulating the immune system to advance the treatment paradigm in cancer.”
In February, Merck announced that it had entered into agreements with subsidiaries of Amgen, Incyte, and Pfizer for the evaluation of the PD-1 inhibitor pembrolizumab (MK-3475). Through this collaboration, pembrolizumab will be explored in combination with axitinib in RCC, talimogene laherparepvec in previously untreated advanced melanoma, the immunotherapy INCB24360 in previously treated metastatic recurrent NSCLC, and PF-2566 in multiple cancer types.
The FDA assigned a priority review designation to pembrolizumab as a potential treatment for patients with unresectable or metastatic melanoma following progression on ipilimumab in May 2014. As part of this review program, the FDA will make a decision on the drug by October 28, 2014.Illumina is developing a next-generation sequencing (NGS)-based companion diagnostic that will be utilized for treatment selection across a variety of clinical trials investigating therapies from AstraZeneca (AZ), Janssen Biotech, and Sanofi.
The collaborative clinical trials will utilize Illumina's MiSeqDX NGS platform, which received FDA approval in November 2013 for patients with cystic fibrosis. This system isolates and copies specific genes from blood samples that are then analyzed using custom software.
NGS allows for high throughput gene sequencing, which provides more information than traditional single-analyte diagnostics. The efficacy of the MiSeqDX platform was validated across various genomic segments from 19 chromosomes, according to the FDA. This broad range of efficacy allows for a single NGS-based assay to effectively serve as a companion diagnostic across multiple indications.
“This partnership has the potential to deliver an unprecedented amount of clinical information from a single test. Illumina’s technology will inform doctors about the molecular make-up of their patients’ tumors, enabling them to match medicines to the drivers of disease," Ruth March, the vice president of Personalized Healthcare & Biomarkers at AstraZeneca, said in a statement. "Our aim is that doctors can use these tests to prescribe the right drugs to the right patients — bringing benefits to healthcare professionals, payers and patients alike.”
Following the test’s approval in 2013, Illumina sought to strengthen its ability to market and develop the NGS test through the acquisition of Myraqa, a consulting firm focused on in vitro diagnostics, including companion diagnostics. At the time of the purchase, Illumina made it clear that Myraqa's expertise would guide the company's regulatory strategies and applications.Late last month, AstraZeneca and Roche announced a partnership focused on the development of a companion diagnostic for the next-generation EGFR inhibitor AZD9291, which is an irreversible inhibitor of the T790M acquired resistance mutations.
Up to 60% of patients with NSCLC treated with a frontline EGFR inhibitor acquire a mutation in T790M, making it the leading cause of resistance. Given the nature of the mutation, a repeat biopsy is required in order to detect the alteration. However, tissue is difficult to collect in this population.
To address this concern, a companion diagnostic test will be designed to detect the T790M mutation in circulating DNA from plasma samples, allowing for the avoidance of a repeat biopsy in patients with metastatic NSCLC.
“Currently, late-stage lung cancer patients have to undergo surgery to collect tissue from a tumor so it can be sent for molecular testing,” Paul Brown, head of Roche Molecular Diagnostics, said in a release. “In some cases, collecting enough tissue for testing is not possible. This collaboration will enable molecular testing through plasma specimens and provide the information needed to inform treatment decisions without the complications of surgery, consequently increasing the level of care clinicians can give to the patient.”