On September 7, 2016 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that it has reached its enrollment target of 132 patients for the company’s global Phase 2b clinical trial of aldoxorubicin in patients with previously treated small cell lung cancer (SCLC) (Press release, CytRx, SEP 7, 2016, View Source [SID:1234514980]). The Phase 2b study is a randomized, comparative trial being conducted at 41 sites in the United States, Hungary and Spain.

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!

"Patients with metastatic small cell lung cancer who have relapsed or are refractory to first-line chemotherapy have few treatment options," said Steven A. Kriegsman, Chairman and CEO of CytRx. "Aldoxorubicin represents a potential new therapy to combat this aggressive form of cancer. The Phase 2b trial uses a lower dose of aldoxorubicin than our Phase 3 trial in soft tissue sarcoma, which may improve the tolerability and potentially allow patients to stay on treatment longer. We look forward to reporting the trial results once they are available."

Because of the unmet medical need for patients with second-line SCLC, if the global Phase 2b clinical trial results are positive, CytRx intends to meet with the U.S. FDA to discuss the regulatory pathway for the submission of a New Drug Application for aldoxorubicin in this patient population.

Trial Design

The multicenter, randomized, open-label, global Phase 2b clinical trial enrolled 132 patients with metastatic SCLC who either did not respond to, or who progressed following treatment with one systemic therapy. Trial patients were randomized 1:1 to be treated with aldoxorubicin at a dose of 230mg/m2 (170mg/m2 of doxorubicin equivalents) or standard dose topotecan. The primary endpoint of the study is progression-free survival, and secondary endpoints include overall survival, response rates and safety.

About Small Cell Lung Cancer

An estimated 1.6 million new cases of lung cancer are diagnosed worldwide each year. In the Western world, approximately 13-15% of cases are SCLC, a deadly form of lung cancer associated with tobacco use. The five-year survival rate is less than 7%, in part, because an estimated 70% of patients have extensive disease at diagnosis. According to the American Cancer Society, more than 33,000 new cases will be diagnosed in the USA in 2016. GlobalData estimates the 2016 incidence of SCLC in Europe and Asia to be greater than 32,000 and 175,000, respectively.

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 dosing 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, global Phase 2b clinical trial in first-line STS.

On September 7, 2016 Agios Pharmaceuticals, Inc. (the "Company") reported that its collaboration partner Celgene Corporation ("Celgene") expects to submit a new drug application ("NDA") to the U.S. Food and Drug Administration ("FDA") for enasidenib (AG-221), a first-in-class, oral, selective, potent inhibitor of mutant isocitrate dehydrogenase-2 ("IDH2"), in relapsed and/or refractory acute myeloid leukemia ("AML") (Filing, 8-K, Agios Pharmaceuticals, SEP 7, 2016, View Source [SID:1234514978]).

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!

The NDA will be based on data from the ongoing phase 1/2 study of AG-221 in patients with advanced hematologic malignancies with an IDH2 mutation. The NDA submission is expected to occur by year-end 2016. Celgene will be discussing the planned enasidenib NDA submission at the Citi 11th Annual Biotech Conference in Boston in a webcast event on Wednesday, September 7, 2016 at 12:00 pm ET.

Patients with isocitrate dehydrogenase 1 ("IDH1") mutant-positive AML whose disease has progressed after standard therapies also have limited treatment options, and the Company plans to explore a similar regulatory path for AG-120, its wholly-owned, first-in-class, oral, potent inhibitor of mutant IDH1, which could lead to a NDA submission in 2017 in the U.S. The Company plans to provide a regulatory update on AG-120 by the end of 2016.

The ongoing AG-221 phase 1/2 trial includes a dose-escalation phase and the following five expansion cohorts, all of which have completed accrual: (i) a cohort of 25 patients aged 60 years or older with IDH2 mutant-positive relapsed or refractory AML, or any IDH2-mutant positive AML patient, regardless of age, who has relapsed following a bone marrow transplant ("BMT"); (ii) a cohort of 25 patients aged less than 60 years with IDH2 mutant-positive relapsed or refractory AML, not including patients with AML who have relapsed following a BMT; (iii) a cohort of 25 patients aged 60 years or older with untreated IDH2 mutant-positive AML who decline standard of care chemotherapy; (iv) a cohort of 25 patients with IDH2 mutant-positive advanced hematologic malignancies not eligible for cohorts (i) to (iii); and (v) a cohort of approximately 125 patients with IDH2 mutant-positive AML who are in second or later relapse, refractory to second-line induction or reinduction treatment, or have relapsed after allogeneic transplantation.

On September 7, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX) reported that it has entered into a collaboration with Genentech, a member of the Roche Group, to support several Phase 1b studies investigating BioLineRx’s BL-8040 in combination with Atezolizumab, Genentech’s anti-PDL1 cancer immunotherapy, in multiple cancer indications (Press release, BioLineRx, SEP 7, 2016, View Source [SID:1234514964]). The Phase 1b studies will evaluate the clinical response, safety and tolerability of the combination of these therapies, as well as multiple pharmacodynamic parameters, in hematologic malignancies and solid tumors.

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!

Under the agreement, Genentech will sponsor and conduct several Phase 1b trials in multiple solid cancer indications. In addition, BioLineRx will sponsor and conduct a Phase 1b study in acute myeloid leukemia (AML) patients. The studies are planned as open-label, multicenter, single-arm trials designed to evaluate the safety and efficacy of the combination of BL-8040 and Atezolizumab. Upon completion of the studies, both parties will have the option to expand the collaboration to include a pivotal registration study. Additional details of the collaboration were not disclosed.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the migration of anti-tumor T cells into the tumor micro-environment. Atezolizumab is a humanized monoclonal antibody designed to bind with a protein called PD-L1. Atezolizumab is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7-1 (CD80) receptors. By inhibiting PD-L1, Atezolizumab may enable the activation of T cells, whose migration into the tumor may be enhanced by BL-8040.

"This collaboration agreement in multiple cancer indications with Genentech marks our second collaboration with a world leader in cancer immunotherapy for the combination of BL-8040 with an approved immune checkpoint inhibitor," stated Philip Serlin, Chief Financial and Operating Officer of BioLineRx. "Immune checkpoint inhibitors are a new class of promising drugs that have revolutionized anti-cancer treatment; however, it is becoming clear that certain tumor types will require a combination of immunotherapy with other classes of drugs. We are hopeful that the combination of BL-8040 and Atezolizumab will demonstrate the potential to expand the benefit of immunotherapy to cancer types currently resistant to cancer immunotherapy treatments."

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.