1stOncology™: Cancer Intelligence Service – Page 15608 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Calithera Biosciences Reports CB-839 Phase I Renal Cell Carcinoma Combination Data at the 28th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics

On November 29, 2016 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that clinical data from its lead product candidate CB-839, a first-in-class glutaminase inhibitor, will be presented in a plenary session at the 28th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany (Press release, Calithera Biosciences, NOV 29, 2016, View Source [SID1234516840]). The data demonstrate the clinical activity, tolerability and unique mechanism of action of CB-839 in patients with renal cell carcinoma.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"CB-839 is the first tumor metabolism drug to target a pathway that starves cancer cells by directly depriving them of a key nutrient. We are pleased to present combination data of CB-839 with everolimus that demonstrates high rates of disease control with a well-tolerated combination therapy," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

Dr. Funda Meric-Bernstam from MD Anderson Cancer Center will present in a plenary session, "Phase I study of CB-839, a small molecule inhibitor of glutaminase, in combination with everolimus in patients with clear cell and papillary renal cell carcinoma." As of October 25, 2016, 15 renal cell carcinoma patients were treated and evaluable for response, including 12 clear cell patients, and three papillary patients. Ninety-three percent (93%) have disease control; one patient has a partial response, one patient has progressive disease, and 13 patients have stable disease. The median progression free survival is 8.5 months and for the majority of patients, their time on therapy is longer than their time on treatment in their prior therapy. In the clear cell patient population the disease control rate is 100% and eight patients remain on study. For comparison, in a separate trial of everolimus vs. cabozantinib, the progression free survival of patients in the everolimus group from the Meteor Phase 3 study in second and third line patients was 3.9 months.1

Patients enrolled in the trial had advanced or metastatic disease and had received a median of two prior treatments, which included tyrosine kinase inhibitors, mTOR inhibitors, and checkpoint inhibitors. Patients were administered CB-839 in oral doses that ranged from 400-800 mg twice a day in combination with a fixed oral dose of everolimus at 10 mg once a day. The addition of CB-839 to full dose everolimus has been well tolerated, with a similar safety profile to the known profile of everolimus alone. Grade 3 events include two events of hyperglycemia and one event each of diarrhea, anemia and fatigue. On the basis of this efficacy and safety data, the company plans to continue development in combination therapy for clear cell renal cell carcinoma. Clear cell is the most common form of kidney cancer comprising 75%-85% of cases.

In addition, the following poster presentations will be presented at the meeting:

CB-839, a selective glutaminase inhibitor, has anti-tumor activity in renal cell carcinoma and synergizes with everolimus and receptor tyrosine kinase inhibitors
Session: Molecular targeted agents II, December 1, 2016
Arginase inhibitor CB-1158 elicits immune-mediated anti-tumor responses as a single agent and enhances the efficacy of other immunotherapies
Session: Immunotherapy, November 30, 2016
1 Choueiri, T, Escudier, B. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. The Lancet 2016 July; 17: 917-927.

Chi-Med to Present Data from Proof-of-Concept Clinical Trials for Fruquintinib and Epitinib at the 17th World Conference on Lung Cancer (“WCLC”)

On November 29, 2016 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that results from two non-small cell lung cancer ("NSCLC") clinical studies will be presented at WCLC in Vienna, Austria, from December 4 to 7, 2016 (Press release, Hutchison China MediTech, NOV 29, 2016, View Source [SID1234516838]). Results from the positive Phase II third-line NSCLC clinical trial of fruquintinib, a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors ("VEGFR"), will be detailed in an oral presentation. Results from the ongoing Phase Ib first-line NSCLC clinical trial of epitinib, a highly selective inhibitor of the epidermal growth factor receptor ("EGFR") designed to optimize brain penetration, will also be presented.

In September 2015, Chi-Med announced that the fruquintinib Phase II NSCLC clinical trial had successfully achieved its primary endpoint. The oral and poster presentations will include more mature data than those included in the following fruquintinib and epitinib study abstracts.

The results of the two studies will be presented in detail at WCLC as follows:

Type: Oral Presentation
Title: A Randomized, Multi-Center, Double-Blind Phase II Study of Fruquintinib in Patients with Advanced Non-Small Cell Lung Cancer
Presenter: Shun Lu
Abstract: #4571
Session: OA11 – Angiogenesis in Advanced Lung Cancer, Oral Session
Date & Time: Tuesday, December 6, 2016 (11:00 AM – 12:30 PM)
Type: Poster Presentations
Title: A Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain Metastasis
Authors: Qing Zhou, et al.
Abstract: #4253
1st Session: JCES01 Joint IASLC–Chinese Society for Clinical Oncology /
Chinese Alliance Against Lung Cancer Session (ID 413)
Date & Time: Sunday, December 4, 2016 (10:30 AM – 11:30 AM)
2nd Session: 07. Advanced NSCLC
P2.03b – Poster Session with Presenters Present (ID 465)
Date & Time: Tuesday, December 6, 2016 (2:30 PM – 3:45 PM)
The WCLC presentations will be made available for download at www.chi-med.com/news on the following day.

Organized by the International Association for the Study of Lung Cancer (IASLC) and held annually, WCLC is a global, multidisciplinary scientific forum for sharing current knowledge and research progress in lung cancer. For more information, please visit: wclc2016.iaslc.com.

VBL Therapeutics Announces Overall Survival Data for VB-111 Monotherapy in Phase 2 Study for Recurrent Thyroid Cancer

On November 29, 2016 VBL Therapeutics (NASDAQ:VBLT), reported top-line results from its exploratory Phase 2 study of VB-111 (ofranergene obadenovec) in patients with advanced, differentiated thyroid cancer (Press release, VBL Therapeutics, NOV 29, 2016, View Source [SID1234516836]). As previously announced, this trial met its primary endpoint, which was defined as 25% progression-free survival at 6 months (PFS-6), in heavily-pretreated patients with late-stage disease. A dose-dependent response was seen, with 35% of patients reaching PFS-6 in the therapeutic dose cohort, versus 25% in a low-dose cohort. Given this positive clinical response, the Company continued to follow patients for overall survival (OS) data, which was not a primary endpoint. Although the trial included a small number of patients and was not powered to show OS differences, the new data show a dose-response and evidence of an overall survival benefit in the cohort of patients treated with multiple therapeutic doses of VB-111, compared to patients who received a single low dose of VB-111 (mOS 761 days versus 469 days; p=0.096). Only one patient remained alive in the low-dose cohort, compared to a tail of about 50% in the high dose group.

"The appearance of dose-dependent superior overall survival provides encouragement, especially given that this trial enrolled patients with late-stage disease whose tumors were resistant to multiple lines of previous therapies," said Keith C. Bible, MD, PhD, Professor of Oncology, Division of Medical Oncology, Department of Oncology, and Endocrine Malignancies Disease Oriented Group, Mayo Clinic Cancer Center, and Primary Investigator for this trial.

"This is the third indication in which we have seen profound clinical responses and evidence of an overall survival benefit with VB-111," said Dror Harats, MD, Chief Executive Officer of VBL Therapeutics. "Following our Phase 2 OS data in recurrent GBM and platinum-resistant ovarian cancer, this trial, which evaluated VB-111 as monotherapy, reinforces the potential of VB-111 and its unique mechanism of action, for multiple solid tumor indications. We are continuing to focus on completion of our clinical program, and potentially commercialization, of VB-111 for rGBM, and to advance our ovarian cancer clinical program. Based on the current data, we may expand our program to additional indications, such as thyroid cancer, either independently in the future, or earlier in collaboration with a strategic partner," added Prof. Harats.

The open-label dose-escalating study enrolled patients with advanced, recently-progressive, differentiated thyroid cancer that is unresponsive to radioactive iodine, in two cohorts. The majority of patients had tumors which had failed on several therapeutic lines, including tyrosine kinase inhibitors, prior to enrollment. In the first cohort twelve patients received a single intravenous infusion of VB-111 at a low dose of 3X1012 viral particles (VPs). The second cohort included seventeen patients, who received VB-111 at a therapeutic dose of 1013 VPs every two months until disease progression. The company previously reported that 35% of patients in the therapeutic dose cohort (n=17) met the primary endpoint of 6-month progression-free survival using Response Evaluation Criteria in Solid Tumors (RECIST), compared to 25% of patients in the low dose cohort. PFS at 12 months was 25% in the VB-111 high dose cohort, versus 0% in the low dose cohort. Continued follow-up now indicates further survival benefit for the multiple-dose therapeutic cohort, with median OS of 761 versus 469 in the low-dose cohort (p=0.096). VB-111 was well-tolerated in this study, with no signs of clinically significant safety issues.

About Thyroid Cancer
Thyroid cancer occurs in the thyroid gland, a hormone-producing organ at the base of the neck that regulates heart rate, blood pressure, body temperature and weight. According to the National Cancer Institute, there are an estimated 535,000 people currently living with thyroid cancer in the United States, with an estimated 60,000 new cases each year and an estimated 1,850 annual deaths as a result of the disease. The type of treatment depends on the cancer cell type, tumor size and severity of the disease. First-line treatment is surgical removal of the thyroid gland, and is recommended for most patients. Treatment with radioactive iodine after surgery to destroy any remaining thyroid tissue may be recommended for more advanced disease. If radioactive iodine is ineffective, other treatments are prescribed, such tyrosine kinase inhibitors and systemic chemotherapy. However, if such treatments are unsuccessful, the therapeutic options for patients are currently very limited.

FDA Accepts the Biologics License Application for Avelumab for the Treatment of Metastatic Merkel Cell Carcinoma for Priority Review

On November 29, 2016 EMD Serono Inc., the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the US and Canada, and Pfizer Inc. (NYSE: PFE (link is external)) reported that the US Food and Drug Administration (FDA) has accepted for Priority Review EMD Serono’s Biologics License Application (BLA) for avelumab (Press release, Pfizer, NOV 29, 2016, View Source [SID1234516831]). This review relates to avelumab’s proposed use in patients with metastatic Merkel cell carcinoma (MCC), based on tumor response results from the JAVELIN Merkel 200 trial. Avelumab is an investigational fully human anti-PD-L1 IgG1 monoclonal antibody and could be the first treatment indicated for metastatic MCC in the US, if approved.[*] MCC is a rare and aggressive skin cancer, which impacts approximately 2,500 Americans a year.[1],[2]

"We are pleased the FDA has granted a Priority Review designation for avelumab," said Luciano Rossetti, M.D., Executive Vice President, Global Head of Research & Development at the biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "There are currently no approved treatment options for metastatic MCC, and we are committed to working with the FDA to potentially bring the first approved cancer immunotherapy to patients with this aggressive disease."

The avelumab metastatic MCC BLA submission is supported by data from JAVELIN Merkel 200, a multicenter, single-arm, open-label, Phase II study of 88 patients with metastatic MCC, whose disease had progressed after at least one chemotherapy treatment.[1] The JAVELIN Merkel 200 study represents the largest data set of any anti-PD-L1/PD-1 antibody reported in this patient population. These data were presented in June 2016 at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and published in the Lancet Oncology in October 2016.[1]

"Metastatic Merkel cell carcinoma is an aggressive disease, and patients face a very poor prognosis, with less than 20 percent surviving beyond five years," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "We are encouraged by the results of our Phase II trial and believe avelumab may have potential to be an important treatment option for patients living with this hard-to-treat skin cancer."

The FDA’s Priority Review status reduces the review time from 10 months to a goal of six months from the day of filing and is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. The FDA previously granted avelumab Orphan Drug Designation for MCC, as well as Fast Track and Breakthrough Therapy Designations for the treatment of patients with metastatic MCC whose disease has progressed after at least one previous chemotherapy regimen. Breakthrough Therapy Designation is intended to expedite the development and review of treatments for serious or life-threatening disease where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies for one or more endpoints.[3] Additionally, the European Medicines Agency has validated for review Merck KGaA, Darmstadt, Germany’s Marketing Authorization Application (MAA) for avelumab, for the proposed indication of metastatic MCC.

The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 3,000 patients evaluated across more than 15 different tumor types. In addition to metastatic MCC, these cancers include breast, gastric/gastroesophageal junction, head and neck, Hodgkin’s lymphoma, melanoma, mesothelioma, non-small cell lung, ovarian, renal cell carcinoma and urothelial (primarily bladder).

*Avelumab is not approved for any indication in any market. This marks the first acceptance of an application by the US FDA to review the investigational product, avelumab.

CytRx Reports Statistically Significant Updated Results from Pivotal Phase 3 Trial of Aldoxorubicin in Patients with Second-Line Soft Tissue Sarcomas

On November 29, 2016 CytRx Corporation (NASDAQ: CYTR) reported positive updated results from its pivotal Phase 3 clinical trial evaluating aldoxorubicin compared to investigator’s choice in patients with relapsed or refractory soft tissue sarcomas (STS) (Press release, CytRx, NOV 29, 2016, View Source [SID1234516830]).

The study, which enrolled 433 patients, demonstrated a statistically significant improvement in progression-free survival (PFS) between aldoxorubicin and investigator’s choice therapy in 246 patients with leiomyosarcoma and liposarcoma, (p=0.007). The hazard ratio (HR) was 0.62 (95% CI 0.44-0.88), representing a 38% reduction in the risk of tumor progression for patients receiving aldoxorubicin versus investigator’s choice. Leiomyosarcoma and liposarcoma are the two most common types of STS and accounted for 57% of the patients enrolled in the trial.

Aldoxorubicin demonstrated a statistically significant improvement in PFS over investigator’s choice in 312 patients treated in North America (p=0.028; HR=0.71, 95% CI 0.53-0.97). Notably, aldoxorubicin performed better than investigator’s choice for the entire study population and narrowly missed statistical significance (p=0.12; HR=0.81, 95% CI 0.64-1.06). All responses were determined by an independent, blinded central lab assessment of scans.

"This data represents a major step forward for STS, a rare, highly complex and very difficult-to-treat group of cancers," commented Sant Chawla, M.D., F.R.A.C.P., Director of the Sarcoma Oncology Center in Santa Monica, California, and Principal Investigator for the Phase 3 trial. "These results are important because they demonstrate that treatment with aldoxorubicin can extend the time to progression in a clinically meaningful way. The trial design used was more stringent than any prior clinical trial in STS as it compared aldoxorubicin to real world alternatives. The control arm allowed trial investigators to select any one of the five most widely used treatments best suited for their patients’ specific type of STS. Unlike other clinical trials for relapsed or refractory STS which used either dacarbazine or placebo as the control, this study was biased in favor of choosing the best therapy for the patients, a truly unique study design."

CytRx plans to submit the results of this clinical trial for presentation at an upcoming major scientific meeting.

In the entire study population, aldoxorubicin achieved a statistically significant improvement in the disease control rate (DCR; defined as objective response rate (ORR) plus stable disease for at least 4 months) of 29.4% versus 20.5% for the patients treated with investigator’s choice (p=0.030). In North American patients, the benefit was even more pronounced with aldoxorubicin-treated patients exhibiting a DCR of 32.9%, compared to 19.2% for patients treated with investigator’s choice (p=0.007), an overall improvement of 71%. ORR in North American patients also favored aldoxorubicin over investigator’s choice, 8.7% versus 3.3% (p=0.058). Of note, no objective responses were observed in patients treated with Votrient (pazopanib). Patients continue to be followed for overall survival (OS), a secondary endpoint, and CytRx expects the OS data to be available in 2017.

PFS, DCR and ORR data are summarized in the following table:

Phase 3 Aldoxorubicin Efficacy Results

N
Aldoxorubicin
Investigator’s Choice
P Value
All patients with Leiomyosarcoma and Liposarcoma (PFS)

246
HR = 0.62 (95% CI 0.44-0.88)
0.007

North American1 patients (PFS)

312
HR = 0.71 (95% CI 0.53-0.97)
0.028
Disease Control Rate (DCR)2

32.9%
19.2%
0.007
Objective Response Rate (ORR)

8.7%
3.3%
0.058
All patients (PFS)

433
HR = 0.81 (95% CI 0.64-1.06)
0.120
Disease Control Rate (DCR)2

29.4%
20.5%
0.030

1Per trial statistical analysis plan, North America is defined as United States, Canada and Australia and comprises 72% of total trial patients
2DCR=ORR + stable disease for ≥4 months
Pre-specified analyses were based on sarcoma histopathology and geography. The geographic analysis includes patients from North America (defined as the United States, Canada and Australia, per the trial statistical analysis plan). The 312 patients treated in North America comprise 72% of the total trial population, including 296 patients from the United States, 8 patients from Canada and 8 patients from Australia. The 246 patients with leiomyosarcoma or liposarcoma comprise 57% of the total trial population.

Aldoxorubicin did not cause clinically significant cardiac, renal, or hepatic toxicities. For the global trial population, the most commonly reported adverse events were neutropenia and anemia consistent with prior clinical trials with aldoxorubicin. Grade 3 or higher hypertension occurred in patients receiving Votrient (pazopanib). Grade 3 or higher adverse events were manageable with supportive care and occurred at a rate of 61% for patients receiving aldoxorubicin and 46% in patients treated with investigator’s choice. Importantly, treatment-emergent adverse events leading to discontinuation occurred in 4.2% of patients treated with aldoxorubicin, compared to 6.3% for patients receiving investigator’s choice. Serious adverse events, primarily febrile neutropenia that resolved and rarely led to treatment termination occurred more frequently in patients administered aldoxorubicin. Treatment-related deaths occurred in one aldoxorubicin-treated patient and in no patients receiving investigators’ choice drugs.

Based on these results, CytRx expects to submit a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for aldoxorubicin as a treatment for patients with relapsed or refractory STS in 2017.

"These results show that globally leiomyosarcoma and liposarcoma patients treated with aldoxorubicin exhibited significantly longer PFS than patients treated with both FDA-approved and commonly used therapies in the second-line setting," said Daniel Levitt, M.D., Ph.D., EVP and Chief Medical Officer of CytRx. "We are also very encouraged by the statistically significant improvements observed in North American STS patients treated with aldoxorubicin who exhibited both longer PFS and superior response rates."

"We are deeply grateful for the support and commitment of the sarcoma investigators, along with the patients and families who took part in or contributed to this Phase 3 trial," stated Steven A. Kriegsman, CytRx’s Chairman and Chief Executive Officer. "We look forward to sharing the data from these key patient populations with the FDA to support an NDA for aldoxorubicin as a second-line treatment for patients suffering with soft tissue sarcomas."

About the Phase 3 Clinical Trial

The randomized, controlled Phase 3 trial enrolled a total of 433 patients at 79 clinical sites. Patients with metastatic, locally advanced or unresectable soft tissue sarcomas who had either not responded to, or who had progressed following treatment with one or more systemic regimens of non-adjuvant chemotherapy were randomized 1:1 to be treated with aldoxorubicin or the investigator’s choice of an approved chemotherapeutic regimen, including doxorubicin, ifosfamide, dacarbazine, pazopanib (Votrient), or gemcitabine plus docetaxel. The primary endpoint of the study is PFS. Secondary endpoints include overall survival, response rates, disease control rates and safety.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. It can arise anywhere in the body at any age. STS remains a high unmet medical need because of the difficulty in treating the more than 50 types of this aggressive cancer. According to the American Cancer Society, in 2016 more than 12,300 new cases were diagnosed in the U.S. and approximately 5,000 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.

About Aldoxorubicin

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line STS.