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FORMA THERAPEUTICS ENROLLS FIRST PATIENT IN PHASE 1 STUDY OF FT-1101 IN ADVANCED HEMATOLOGICAL MALIGNANCIES

On January 12, 2016 FORMA Therapeutics reported the initiation of a Phase 1 study of FT-1101, with the first dose administration in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234511394]). FT-1101 is an oral, structurally distinct and potent pan-inhibitor of the BET (Bromodomain and Extra-Terminal) epigenetic protein family.

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"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome"
"The BET protein family represents an attractive group of therapeutic targets for a variety of liquid and solid tumors, as inhibition of these epigenetic binding proteins allows for selective effects on gene expression. FT-1101 is a novel, oral small molecule targeted against all four BET family members (BRD2, BRD3, BRD4, BRDT)," said John Hohneker, M.D., EVP and Head of Research and Development, FORMA Therapeutics. "The launch of this study is an important step for our team, and we are eager to begin the selection of preferred dosing schedules and potential patient populations in order to optimize activity and tolerability of this novel medicine."

Small molecule inhibition of BET results in down-regulation of the critical oncogene MYC, a master regulator of diverse cell functions critical for cell growth and survival in many cancers. At tolerated doses in human tumor xenograft mouse models, FT-1101 has demonstrated significant anti-tumor activity including tumor regressions.

FT-1101 is part of FORMA’s second global strategic collaboration with Celgene Corporation announced in April 2014. Celgene has obtained an exclusive EU license for FT-1101 in exchange for an undisclosed payment to FORMA. Under the terms of the collaboration agreement, FORMA will advance the FT-1101 program through Phase 1, and Celgene will be responsible to fund and execute further global clinical development.

"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome," said Guillermo Garcia-Manero, M.D., lead clinical investigator for FT-1101 at The University of Texas MD Anderson Cancer Center, Houston, TX, and Professor, Department of Leukemia, Division of Cancer Medicine.

About the Study

The Phase 1 multicenter, open-label, dose escalation clinical trial is designed to assess the safety and tolerability of FT-1101 capsules as a single agent. FT-1101 will be administered orally on a once weekly dosing schedule in a 28-day cycle. The study will enroll patients with relapsed refractory AML and high risk myelodysplastic syndrome. Key objectives in the study include determination of a maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of FT-1101. Please refer to www.clinicaltrials.gov for additional clinical trial details.

About BET

The Bromodomain and Extra-Terminal (BET) family of bromodomain-containing proteins (BRD2, BRD3, BRD4, and BRDT) regulate chromatin structure and gene expression through their ability to bind to acetylated lysine residues on histone tails and act as epigenetic readers. In particular, BRD4 has been shown to positively regulate the expression of MYC and other critical cancer-associated genes through the localization of BRD4 to super-enhancer regulatory elements. Preclinical studies conducted using BET inhibitors and emerging data from ongoing clinical trials in leukemia and lymphoma patients, have provided initial support for the therapeutic potential of BET inhibitors in hematologic malignancies.

FORMA THERAPEUTICS ENROLLS FIRST PATIENT IN PHASE 1 STUDY OF FT-1101 IN ADVANCED HEMATOLOGICAL MALIGNANCIES

On January 12, 2016 FORMA Therapeutics report the initiation of a Phase 1 study of FT-1101, with the first dose administration in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234509342]). FT-1101 is an oral, structurally distinct and potent pan-inhibitor of the BET (Bromodomain and Extra-Terminal) epigenetic protein family.

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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

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"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome"

"The BET protein family represents an attractive group of therapeutic targets for a variety of liquid and solid tumors, as inhibition of these epigenetic binding proteins allows for selective effects on gene expression. FT-1101 is a novel, oral small molecule targeted against all four BET family members (BRD2, BRD3, BRD4, BRDT)," said John Hohneker, M.D., EVP and Head of Research and Development, FORMA Therapeutics. "The launch of this study is an important step for our team, and we are eager to begin the selection of preferred dosing schedules and potential patient populations in order to optimize activity and tolerability of this novel medicine."

Small molecule inhibition of BET results in down-regulation of the critical oncogene MYC, a master regulator of diverse cell functions critical for cell growth and survival in many cancers. At tolerated doses in human tumor xenograft mouse models, FT-1101 has demonstrated significant anti-tumor activity including tumor regressions.

FT-1101 is part of FORMA’s second global strategic collaboration with Celgene Corporation announced in April 2014. Celgene has obtained an exclusive EU license for FT-1101 in exchange for an undisclosed payment to FORMA. Under the terms of the collaboration agreement, FORMA will advance the FT-1101 program through Phase 1, and Celgene will be responsible to fund and execute further global clinical development.

"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome," said Guillermo Garcia-Manero, M.D., lead clinical investigator for FT-1101 at The University of Texas MD Anderson Cancer Center, Houston, TX, and Professor, Department of Leukemia, Division of Cancer Medicine.

FORMA THERAPEUTICS AND CANCER RESEARCH TECHNOLOGY FORM A THIRD VIRTUAL COMPANY TO ADVANCE DEUBIQUITINATION ASSETS

On January 11, 2016 FORMA Therapeutics and Cancer Research Technology, reported the formation of a third new virtual Asset Discovery and Development Company (ADDCos) with novel chemical matter targeting an undisclosed deubiquitinating enzyme (DUB) (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234509341]). ADDCos are virtual companies that rapidly advance drug discovery innovations in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

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This achievement is the result of an ongoing long-term initiative between FORMA and Cancer Research Technology, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under the agreement, FORMA is pairing its ultra-efficient drug discovery and early development capabilities with expertise from Cancer Research Technology’s Discovery Laboratories and the exclusive world-class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when aberrantly dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to represent highly attractive discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "The evolution of R&D across a distributed network of diverse scientific disciplines allows FORMA to rapidly and creatively advance research discoveries into clinical candidates."

Keith Blundy, CEO of Cancer Research Technology, said: "This partnership has proven to yield exciting biology and translational outcomes, when pairing complementary skills and capabilities together within a unique business structure. We look forward seeing such research discoveries develop into new medicines offering breakthrough treatments to cancer patients worldwide."

FORMA Therapeutics and CRT form a third virtual company to advance deubiquitination assets

On January 12, 2016 FORMA Therapeutics and Cancer Research Technology reported the formation of a third new virtual Asset Discovery and Development Company (ADDCos) with novel chemical matter targeting an undisclosed deubiquitinating enzyme (DUB) (Press release, Cancer Research Technology, DEC 12, 2016, View Source [SID1234523189]). ADDCos are virtual companies that rapidly advance drug discovery innovations in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

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!

This achievement is the result of an ongoing long-term initiative between FORMA and Cancer Research Technology, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under the agreement, FORMA is pairing its ultra-efficient drug discovery and early development capabilities with expertise from Cancer Research Technology’s Discovery Laboratories (CRT-DL) and the exclusive world-class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to represent highly attractive discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "The evolution of R&D across a distributed network of diverse scientific disciplines allows FORMA to rapidly and creatively advance research discoveries into clinical candidates."

Keith Blundy, CEO of Cancer Research Technology, said: "This partnership has proven to yield exciting biology and translational outcomes, when pairing complementary skills and capabilities together within a unique business structure. We look forward seeing such research discoveries develop into new medicines offering breakthrough treatments to cancer patients worldwide."

Provectus Biopharmaceuticals Confirms First Patients Dosed in Trials of PV-10 for Melanoma

On January 12, 2015 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus"), reported that patients have been dosed in both its Phase 3 clinical trial of PV-10, Provectus’ novel investigational drug for cancer, for Stage III locally advanced cutaneous melanoma and its Phase 1b/2 clinical trial of PV-10 in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with Stage IV melanoma (Press release, Provectus Pharmaceuticals, JAN 12, 2016, http://www.pvct.com/pressrelease.html?article=20160112.1 [SID:1234508779]). In addition, the Company confirmed that it continues to enroll patients in all of its active oncology studies.

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Eric Wachter, Chief Technology Officer of Provectus, said, "With patients starting treatment in both of these studies, the clock is ticking to interim results and ultimately the completion of these studies. Our recruitment activities are moving ahead and we are hopeful that these studies will play critical roles in demonstrating effectiveness and safety of PV-10 in melanoma."

PHASE 3 STUDY

The Phase 3 study is an international multicenter, open-label, randomized controlled trial (RCT) of single-agent intralesional (IL) PV-10 versus systemic chemotherapy to assess treatment of locally advanced cutaneous melanoma in patients who are BRAF V600 wild-type and have failed or are not otherwise candidates for ipilimumab or another immune checkpoint inhibitor. Subjects in the PV-10 arm receive IL PV-10 to all of their melanoma lesions. Subjects in the comparator arm receive the investigator’s choice of dacarbazine or temozolomide as determined by investigator preference and/or local availability of the agent. Effectiveness will be assessed by comparison of progression-free survival (PFS) between all intent-to-treat (ITT) subjects in the two study arms. The primary outcome measure of PFS is assessed every 12 weeks up to 18 months using RECIST 1.1 criteria. Secondary outcome measures include complete response rate (CRR) and its duration (assessed every 12 weeks up to 18 months); and overall survival (OS) assessed every 12 weeks up to 18 months. Safety and tolerability will be assessed by monitoring the frequency, duration, severity and attribution of adverse events and evaluating changes in laboratory values and vital signs. For more details on the study, please visit View Source

Currently, three sites are recruiting patients, with four additional sites nearing opening of enrollment. Additional sites are in process of being added in the coming weeks.

St. Luke’s Hospital and Health Network, Easton, PA;
Atlantic Health System, Morristown, NJ
University of Louisville, Louisville, KY;
Huntsman Cancer Institute, Salt Lake City, UT; (not yet recruiting),
M.D. Anderson Cancer Center, Houston, TX; (not yet recruiting),
Sharp Memorial Hospital, San Diego, CA; (not yet recruiting),
Princess Alexandra Hospital, Brisbane, Australia; (not yet recruiting).
Dr. Wachter noted, "We are currently finalizing amendments to the protocol that will refine the eligible patient population, consistent with a trial to be expanded this year beyond our historic base in the U.S. and Australia, and to afford additional flexibility in choice of comparator to address the changing treatment options available to patients globally."

PHASE 1b/2 STUDY

The Phase 1b/2 study is an international multicenter, open-label, sequential phase study of intralesional PV-10 in combination with systemic immune checkpoint inhibition. Stage IV metastatic melanoma patients with at least one injectable cutaneous or subcutaneous lesion who are candidates for pembrolizumab are eligible for study participation. In the current Phase 1b portion of the study, all participants will receive the combination of IL PV-10 and pembrolizumab (i.e., PV-10 + standard of care). In the subsequent Phase 2 portion of the study, participants will be randomized 1:1 to receive either the combination of IL PV-10 and pembrolizumab or pembrolizumab alone (i.e., PV-10 + standard of care vs. standard of care).

Up to 24 subjects will be enrolled in the Phase 1b portion of the study. Each subject in this cohort will receive the combination of IL PV-10 and pembrolizumab. The expected completion date is in 2016 for the Phase 1b portion of the study.

A total of an estimated 120 subjects will be randomized in a 1:1 ratio to the two treatment arms (i.e., PV-10 + pembrolizumab or pembrolizumab alone) in the Phase 2 portion of the study. This number of subjects may be modified based on emerging evidence of preliminary efficacy and effect size from the Phase 1b portion of the study.

Subjects assigned to receive PV-10 in Phase 1b and 2 will receive initial IL PV-10 to their injectable cutaneous and subcutaneous lesions commencing on study Day 1 for up to 13 weeks (i.e., the investigational treatment phase of the study). PV-10 may be re-administered at 21-day (3-week) intervals during this period to any remaining, uninjected cutaneous and subcutaneous lesions until all injectable cutaneous and subcutaneous lesions have been injected. Lesions that fail to exhibit complete ablation may be re-injected on this schedule.

Pembrolizumab will be administered at 21-day (3-week) intervals per prescribing information (label) commencing on study Day 1 for up to 24 months or until disease progression, toxicity requiring discontinuation of study treatment or study termination.

Response assessment in both phases of the study will be based on PFS using RECIST 1.1 criteria.

Dr. Wachter added, "Current research suggests that using anti-cancer drugs in combination can have additive or synergistic effects that can improve the outcomes patients experience. KEYTRUDA and PV-10 together may prove more effective than either agent alone in treating certain cases of melanoma. We believe that our current Phase 3 study that tests PV-10 on its own for Stage III patients is designed to prove its effectiveness, but we also believe that we should examine combination therapies to maximize potential benefit to patients, especially those with advanced disease."

The details of the study are available at View Source

For a complete history of Provectus’ research into PV-10 as an investigational treatment for melanoma, visit https://www.pvct.com/pv10melanoma.html.