On January 29, 2015 Celldex Therapeutics and Bristol Myers-Squibb reported the initiation of a Phase 1/2 dose escalation and cohort expansion study examining the investigational combination of varlilumab, Celldex’s CD27 targeting investigational immune-activating antibody and Bristol-Myers Squibb’s immunotherapy Opdivo (nivolumab) (Press release Bristol-Myers Squibb, JAN 29, 2015, View Source [SID:1234501409]). The study will be conducted in adult patients with advanced non-small cell lung cancer (NSCLC), metastatic melanoma (MEL), colorectal cancer (CRC), ovarian cancer, and head and neck squamous cell carcinoma (SCCHN). Varlilumab is a fully human monoclonal antibody that targets CD27, a critical molecule in the activation pathway of lymphocytes. Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells. This study will evaluate the safety and tolerability of the combination and address the hypothesis that the combination of these two mechanisms enhance the anti-tumor activity compared to either agent alone. Celldex is responsible for conducting the study and development costs will be shared.

The Phase 1 dose-escalation portion of the study will assess the safety and tolerability of varlilumab at doses ranging from 0.1 to 10 mg/kg when administered with Opdivo (3mg/kg). Following dose escalation, a Phase 2 portion of the study will include 5 disease specific cohorts, with either 18 (CRC, SCCHN, ovarian) or 35 (NSCLC and MEL) patients in each cohort. Patients will be treated with varlilumab until intolerance, disease progression or completion of up to 4 cycles. There is no limit on the duration of treatment with Opdivo. The primary objective of the Phase 2 study is overall response rate. Secondary objectives include pharmacokinetics assessments, determining the immunogenicity of varlilumab when given in combination with Opdivo and further assessing the anti-tumor activity of combination treatment, including duration of response, time to response, progression-free survival and overall survival.

On January 27, 2015 Amgen and its subsidiary Onyx Pharmaceuticals reported on the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Kyprolis (carfilzomib) for Injection to seek approval for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy (Press release Amgen, JAN 27, 2015, View Source [SID:1234501397]). In the U.S., the sNDA is designed to support the conversion of accelerated approval to full approval and expand the current approved indication. In the European Union (EU), Kyprolis received orphan drug designation and the MAA has been granted accelerated assessment.

The sNDA and MAA are based on data from the Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of Patients with Relapsed Multiple MyEloma) trial and other relevant data.

“Multiple myeloma is an incurable blood cancer that often becomes resistant to treatment, underscoring the need for new therapeutic options that provide deep and durable responses to extend the time patients live without their disease progressing,” said Pablo J. Cagnoni, M.D., president, Onyx Pharmaceuticals, Inc. “The U.S. and EU submissions support our goal of bringing Kyprolis to patients with relapsed multiple myeloma.”

Orphan designation is granted by the EMA for medicines intended for the treatment, prevention or diagnosis of a disease that is life threatening and has a prevalence in the EU of no more than five in 10,000. The intended medicine must aim to provide significant benefit to those affected by the condition.

Kyprolis is in a class of drugs called proteasome inhibitors and was granted accelerated approval by the FDA in 2012. Kyprolis is also approved for use in Argentina, Israel and Mexico.

Opdivo was first approved in July of 2014 in Japan for the treatment of unresectable melanoma and later in December the same year in the US or the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor (Press release Bristol-Myers Squibb, DEC 22, 2014, View Source [SID:1234501237]).

On January 27, 2015 Bristol-Myers Squibb reported accrued sales in US dollars for Opdivo during 2014 (Filing Q4/Annual , Bristol-Myers Squibb, JAN 27, 2015, View Source [SID:1234501395]):
USA: $1M
Non-US (Japan): $5M
Worldwide: $6M