On December 10, 2014 Immunovaccine reported that DPX-Survivac, the Company’s lead cancer vaccine candidate, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) as maintenance therapy in subjects with advanced ovarian, fallopian tube, and peritoneal cancer who have no measureable disease following surgery and front-line platinum/taxane chemotherapy to improve their progression-free survival (Press release Immunovaccine, DEC 10, 2014, View Source [SID:1234501175]). Ovarian cancer patients who have no measurable disease following their initial standard surgery and chemotherapy treatments have an unmet need that may be served by the DPX-Survivac therapy. DPX-Survivac is designed to activate T cells of the immune system that are expected to recognize and eliminate cancer cells in an attempt to keep patients in remission longer.

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs with the potential to treat serious or life-threatening conditions and address an unmet medical need. This designation provides companies the opportunity for more frequent interactions with FDA during clinical development and the “rolling” submission of individual sections of a Biologics License Application (BLA) as they are completed for review by FDA. Additionally, therapies with Fast Track designation are eligible for priority review and/or accelerated approval, which have the potential to reduce the time required for FDA review and make a therapy available to patients earlier than would be traditionally possible.

“This Fast Track designation highlights the urgent need for new, innovative ovarian cancer treatments that can maintain patients in remission longer and ultimately increase survival,” said Dr. Marc Mansour, chief executive officer of Immunovaccine.

Immunovaccine has previously reported positive results from DPX-Survivac clinical studies in ovarian cancer patients. In these studies, robust and durable CD8 T cell responses were observed in almost all patients receiving a specified regimen of the vaccine. The vast majority of ovarian cancer patients enrolled in these studies were in remission with no evidence of disease. Notably, a patient with stable but measurable disease achieved a partial response (PR) as measured by Response Evaluation Criteria In Solid Tumors (RECIST 1.1). The PR, which persisted following discontinuation of treatment, was accompanied by reduction in levels of a commonly used ovarian cancer biomarker (CA125) and a significant increase in vaccine-induced immune responses. The patient benefited from the DPX-Survivac therapy for more than 8 months demonstrating a potentially durable effect of the therapy.

Immunovaccine is finalizing the design of a large randomized Phase II trial in ovarian cancer to be sponsored and conducted by Canada’s NCIC Clinical Trials Group (NCIC CTG).

The company also recently announced that it has received clearance from Health Canada to conduct a Phase II clinical study of DPX-Survivac in patients with diffuse large B cell lymphoma (DLBCL). The Company-sponsored trial, expected to begin in early 2015, will evaluate DPX-Survivac in combination with oral cyclophosphamide, an immune modulating agent, in patients with recurrent DLBCL. Immunovaccine expects initial data from this study in the second half of 2015. Positive trial results could provide rationale for the initiation of a pivotal trial in recurrent DLBCL which could lead to the approval of DPX-Survivac for the treatment of DLBCL.

On December 10, 2014 Merck reported early study findings demonstrating an overall response rate of 18.5 percent with KEYTRUDA, the company’s anti-PD-1 therapy, as assessed by RECIST v1.1, central review (n=5/27), in PD-L1 positive, advanced triple-negative breast cancer – one of the most aggressive forms of breast cancer (Press release Merck & Co, DEC 10, 2014, View Source;0 [SID:1234501156]). At the time of analysis, the median duration of response had not been reached with three of five responders on therapy for 11 months or more (range, 15 to 40+ weeks). These early findings, from the ongoing Phase 1b KEYNOTE-012 study, were shared today for the first time as part of the official press program at the 2014 San Antonio Breast Cancer Symposium (SABCS) (ABSTRACT #S1-09) and will be presented in an oral session at 10:45 a.m. CST by Dr. Rita Nanda, the University of Chicago.

“Metastatic, triple-negative breast cancer is an aggressive and often difficult to treat disease,” said Dr. Rita Nanda, associate director, breast medical oncology, the University of Chicago and principal investigator for the KEYTRUDA triple-negative breast cancer Phase 1b study cohort. “The results presented at this year’s SABCS, while early, show encouraging anti-tumor activity in these patients, most of whom had received multiple prior chemotherapies.”

“This year, Merck has significantly advanced our immuno-oncology development program and new data for KEYTRUDA have been presented in seven different cancers, including these first findings in triple-negative breast cancer,” said Dr. Alise Reicin, vice president, global clinical development, oncology, Merck Research Laboratories. “These early data with KEYTRUDA show responses in patients with one of the most aggressive forms of breast cancer and further our understanding of the PD-1 pathway’s role in this disease. Our Phase 2 study planned for the first half of 2015 will be an important next step for our breast cancer clinical program.”

Early Findings Evaluating KEYTRUDA in Advanced Triple-Negative Breast Cancer

Data presented were from a cohort of the ongoing Phase 1b KEYNOTE-012 study which evaluated KEYTRUDA monotherapy at 10 mg/kg every two weeks in patients with advanced TNBC whose tumors were determined to be positive for PD-L1 expression (n=32). As measured by Merck’s proprietary PD-L1 immunohistochemistry (IHC) clinical trial assay, tumors were considered to be PD-L1 positive if staining was present in the stroma or in greater than or equal to one percent of tumor cells. In the study, 58 percent of patients screened had tumors determined to be positive for PD-L1 expression. Most patients enrolled in this study had received two or more prior chemotherapies for metastatic disease and 87.5 percent had received prior neo-adjuvant or adjuvant therapy.

Antitumor Activity with KEYTRUDA by Response Evaluation Criteria in Solid Tumors
(RECIST) v1.1, Central Review*
Patients Evaluable for Response
(n=27)(a)
Overall Response Rate (ORR), n (%) 5 (18.5%)
Best Overall Response, n (%)
Complete Responseb 1 (3.7%)
Partial Responseb 4 (14.8%)
Stable Disease 7 (25.9%)
Progressive Disease 12 (44.4%)
No Assessmentc 3 (11.1%)

*Analysis cut-off as of: November 10, 2014.

a Includes patients with measurable disease at baseline who received ≥1 pembrolizumab dose and who had ≥1 post-baseline scan or discontinued therapy before the first scan due to progressive disease or a treatment-related AE. Five patients were excluded because they did not have any assessments per central review (n=2) or because they did not have measurable disease per central review at baseline (n=3).

b Confirmed responses only.

c “No assessment” signifies patients who discontinued therapy before the first post-baseline scan due to progressive disease or a treatment-related AE.

The median time to response was 18 weeks (range, 7-32 weeks). In the study, 33 percent of patients with KEYTRUDA achieved tumor shrinkage. At six months, the progression-free survival rate with KEYTRUDA was 23.3 percent.

Adverse events were consistent with previously reported safety data for KEYTRUDA. The most common treatment-related adverse events (occurring in greater than or equal to five percent of patients) included arthralgia (n=6), fatigue (n=6), myalgia (n=5), nausea (n=5), ALT increased (n=2), AST increased (n=2), diarrhea (n=2), erythema (n=2) and headache (n=2). Grade 3-5 treatment-related adverse events occurred in a total of five patients and included anemia, disseminated intravascular coagulation (DIC), headache, meningitis aseptic, decreased blood fibrinogen, and pyrexia. Two patients discontinued KEYTRUDA due to adverse events. One treatment-related death was reported in a patient with rapidly progressive disease and was due to DIC with thrombocytopenia and decreased blood fibrinogen.