On May 27, 2014 Celator Pharmaceuticals reported the publication of the Phase 2 study evaluating CPX-351 in newly diagnosed older patients with acute myeloid leukemia (AML) in Blood, the official journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release Celator Pharmaceuticals, MAY 27, 2014, View Source [SID:1234500554] & Blood. 2014 May 22;123(21):3239-46. doi: 10.1182/blood-2013-12-540971. Epub 2014 Mar 31. View Source). The study manuscript entitled “Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML” appears in the May 22, 2014 issue.
These data, along with results from the Phase 2 study of CPX-351 in patients with AML in first relapse, support Celator’s currently-enrolling Phase 3 study of CPX-351 as a first-line therapy in older patients with high-risk (secondary) AML, which is being conducted in partnership with The Leukemia & Lymphoma Society.
This randomized, controlled, Phase 2 study evaluated 126 patients, aged 60-75 years, from 18 clinical centers in the U.S. and Canada, with newly diagnosed, pathologically confirmed AML. Patients were randomized 2:1 to receive first-line CPX-351 (100 u/m2; days 1, 3, and 5 by 90 minute infusion) or the 7+3 regimen (cytarabine 100 mg/m2/day by continuous infusion for 7 days and daunorubicin 60 mg/m2 on days 1, 2, and 3). The primary endpoint for the study was complete response (CR + CRi) and secondary endpoints included CR+CRi duration, event-free survival and overall survival.
Results showed that CPX-351 treatment was associated with higher complete response rate (66.7% vs. 51.2%; P = 0.07), prolonged event-free survival (median 6.5 vs. 2.0 months) and overall survival (median 14.7 vs. 12.9 months). Ten patients with persistent AML after treatment with 7+3 crossed over to receive CPX-351 as salvage therapy with four achieving response (3 CR + 1 CRi). All four responders survived more than one year and this potentially confounds interpretation of the overall survival data.
A planned analysis of secondary AML patients (patients with a prior antecedent hematologic disorder or history of prior cytotoxic treatment) showed an improved response rate (57.6% vs 31.6%, P=0.06), prolonged event-free survival (median 4.5 vs. 1.3 months, HR=0.59, P=0.08) as well as overall survival (median 12.1 vs. 6.1 months, HR=0.46, P=0.01). The overall survival benefit in this population was statistically significant.
Treatment with CPX-351 was associated with well-characterized and manageable adverse events. Recovery from cytopenias was longer following CPX-351 (median days to ANC ≥1000: 36 vs. 32; Platelets > 100K: 37 vs. 28) with more grade 3-4 infections but without an increase in infection-related deaths (3.5% vs. 7.3%) or 60-day mortality (4.7% vs. 14.6%), indicating acceptable safety.

On May 27, 2014 Bristol-Myers Squibb and Incyte reported the establishment of a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of a combination regimen of Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, nivolumab, and Incyte’s oral indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360, in a Phase I/II study (Press release Bristol-Myers Squibb, MAY 27, 2014, View Source [SID:1234500552]). Multiple tumor types will be explored in the study, which could potentially include melanoma, non-small cell lung (NSCLC), ovarian, colorectal (CRC), squamous cell carcinoma of the head and neck (SCCHN) and diffuse large B-cell lymphoma (DLBCL).
Nivolumab and INCB24360 are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. Nivolumab and INCB24360 target distinct regulatory components of the immune system, and there is preclinical evidence suggesting that the combination of these two agents may lead to an enhanced anti-tumor immune response compared to either agent alone.
The study, which is expected to begin in the fourth quarter of 2014, will be co-funded by the companies and conducted by Incyte. Additional details of the collaboration were not disclosed.

On May 27, 2014 Advaxis reported that it has been granted Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD) for ADXS-cHER2 for the treatment of osteosarcoma (Press release Advaxis, MAY 27, 2014, View Source [SID:1234500551]).
ADXS-cHER2 is an immunotherapy under investigation for targeting the HER2 receptor, which is overexpressed in certain solid-tumor cancers, including bone cancer and breast cancer. Based on strong pre-clinical and canine osteosarcoma clinical data, Advaxis is planning to initiate a clinical development program with ADXS-cHER2 in pediatric patients with osteosarcoma. Pediatric osteosarcoma affects about 400 children and teens in the U.S. every year, representing a small but significant unmet medical need that has seen little therapeutic advancement in decades. Both veterinary and human osteosarcoma specialists consider canine osteosarcoma to be the most analogous disease to human osteosarcoma.

On 23 January 2014, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product Masiviera, intended for the treatment of advanced inoperable pancreatic cancer (Press release , MAY 23, 2014, View Source [SID:1234500537]). The company that applied for authorisation is AB Science.
The applicant requested a re-examination of the opinion. After considering the grounds for this request, the CHMP re-examined the initial opinion, and confirmed the refusal of the marketing authorisation on 22 May 2014.

On May 23, 2014 Roche reported that the EU Committee for Medicinal Products for Human Use (CHMP) recommended that the European Commission approve Gazyvaro in combination with chlorambucil for the treatment of adult patients with previously untreated chronic lymphocytic leukemia (CLL) who have comorbidities making them unsuitable for a certain type of chemotherapy (full-dose fludarabine) (Press release Hoffmann-La Roche, MAY 23, 2014, View Source [SID:1234500534]). Gazyvaro is marketed as Gazyva in the U.S. and the rest of the world.
The CHMP opinion is based primarily on data from the phase III CLL11 study that was conducted in close collaboration with the German CLL Study Group. The study showed that Gazyvaro plus chlorambucil met its primary endpoint by significantly lengthening the amount of time people lived without their disease worsening (progression free survival; PFS) compared to chlorambucil alone and compared to MabThera (rituximab) plus chlorambucil while also increasing the depth of remissions as measured by Minimal Residual Disease (MRD). Gazyvaro plus chlorambucil also increased survival time for previously untreated CLL patients compared to those who received treatment with chlorambucil alone. Data from the study was recently published in the New England Journal of Medicine.
Roche expects a final decision from the European Commission in the coming months.