On June 7, 2017 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported long-term follow-up data from the DYNAMO study, which met its primary endpoint of Overall Response Rate (ORR; p=0.0001) at the final analysis, will be presented at the 14th International Conference on Malignant Lymphoma (ICML), being held June 14-17, 2017 in Lugano, Switzerland (Press release, Verastem, JUN 7, 2017, View Source [SID1234519465]). DYNAMO is a Phase 2 clinical study evaluating the safety and efficacy of duvelisib monotherapy in patients with indolent non-Hodgkin lymphoma (iNHL) who were refractory to both rituximab and chemotherapy or radioimmunotherapy. Duvelisib is an investigational dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma that has demonstrated clinical activity as an oral monotherapy in multiple hematologic cancers, including chronic lymphocytic leukemia (CLL), iNHL, and T-cell lymphoma.

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 long-term follow-up results from the study will be highlighted in an oral presentation titled, "DYNAMO: A Phase 2 Study Demonstrating the Clinical Activity of Duvelisib in Patients with Double-Refractory Indolent Non-Hodgkin Lymphoma," given by Pier Luigi Zinzani, MD, PhD, University of Bologna Institute of Hematology, on Thursday, June 15, 2017 at 15:40 CET (9:40 ET) in Room A, Cinema Corso and Aula Magna (Lugano University).
"The data we are presenting at ICML help fill in the clinical picture for those patients who receive duvelisib over a longer period," noted Dr. Zinzani. "Not only did duvelisib monotherapy continue to show robust and durable responses in double-refractory iNHL, but longer-term exposure to duvelisib did not reveal any unexpected safety findings. These results suggest duvelisib has favorable benefit-risk in double-refractory iNHL, and may provide an important new treatment option for a population in need of new targeted therapies."

Patients enrolled in DYNAMO all had double-refractory iNHL and a median of 3 prior anticancer regimens. Of the 129 patients enrolled, 61 responded (1 complete response [CR], 60 partial responses [PR]), for an overall response rate (ORR) of 47%, as determined by an independent review committee. The ORR in each of the three disease subgroups included: 43% in follicular lymphoma (n=83); 68% in small lymphocytic lymphoma (n=28); and 33% in marginal zone lymphoma (n=18). Responses generally occurred shortly after the start of treatment (median 2 months). Notably, 88% of all patients treated with duvelisib had a reduction in the size of their target lymph nodes. Overall, median duration of response was 10 months, median progression-free survival was 9 months, and median overall survival was 27.8 months.

With additional follow-up (median 18 months), the safety profile of duvelisib monotherapy remains consistent with what has been previously reported in iNHL and other hematologic malignancies. The most common Grade ≥ 3 adverse events were hematologic in nature (neutropenia 30%, thrombocytopenia 15%, anemia 14%). Diarrhea was the most frequently reported nonhematologic adverse event (47%; 15% Grade ≥ 3). As expected in a heavily pretreated and refractory patient population, infections of all types and grades were observed (56%). Pneumonitis and colitis, events previously described with duvelisib, remained relatively uncommon (9% and 5%, respectively). Treatment discontinuations attributed to the most common adverse events were infrequent, suggesting that these events were generally manageable.

"The clinical activity and durability of responses observed in the DYNAMO study seen across a range of highly-refractory disease subtypes, together with the well-characterized and manageable safety profile, highlight the potential of this drug in lymphoid malignancies," said Hagop Youssoufian, MSc, MD, Head of Hematology and Oncology Development at Verastem. "What I find really encouraging, is that we saw these results in patients refractory to both rituximab and chemotherapy, a specific population with unmet medical need."

Following conclusion of Dr. Zinzani’s presentation, a copy of the presentation will be available here.

More About the Phase 2 DYNAMO Study
DYNAMO is a Phase 2, single-arm study, which evaluated the efficacy and safety of duvelisib 25 mg twice daily as monotherapy in 129 iNHL patients, including follicular lymphoma (n=83), small lymphocytic lymphoma (n=28), and marginal zone lymphoma (n=18) whose disease has progressed and are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was ORR as assessed by an independent review committee.

About the Tumor Microenvironment
The tumor microenvironment encompasses multiple tumor and non-tumor cell populations and an extracellular matrix that support cancer cell survival. This includes immunosuppressive regulatory T-cells, myeloid-derived suppressor cells, tumor-associated macrophages, cancer-associated fibroblasts, and extracellular matrix proteins that can hamper the entry and therapeutic benefit of cytotoxic T-cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s product candidates, including duvelisib and defactinib, also target the tumor microenvironment to potentially improve response to therapy.

About Duvelisib
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory CLL,4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory iNHL that achieved its primary endpoint of ORR.5 Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T-cell lymphoma.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

On June 7, 2017 Trillium Therapeutics Inc. (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company, reported that based upon promising early evidence of anti-tumor activity in patients with both myeloid and lymphoid malignancies, it has further expanded its current intravenous dosing trial of TTI-621, an IgG1 SIRPaFc fusion protein targeting CD47 (Press release, Trillium Therapeutics, JUN 7, 2017, View Source [SID1234519464]).

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!

Changes to the trial include:

An additional cohort of patients with Hodgkin lymphoma treated with a combination of TTI-621 and the PD-1 checkpoint inhibitor nivolumab
Two additional cohorts of patients with T- and B-cell acute lymphoblastic leukemia and small cell lung cancer treated with TTI-621 monotherapy
Cautious exploration of dose-intensification, building upon the observation of good overall tolerability associated with attenuated thrombocytopenia over successive weekly doses of TTI-621
Increasing the size of cohorts exhibiting early evidence of clinical benefit
"Having observed meaningful objective responses among multiple treatment-refractory cancer patients, we are now expanding the trial’s scope with additional focused enrollment to extend these preliminary observations and to seek promising new signals of activity—both with TTI-621 monotherapy, with rituximab, and in a novel combination with T-cell checkpoint inhibition," said Trillium’s Chief Medical Officer, Dr. Eric Sievers. "With emerging data linking CD47 blockade with T cell activation, we are excited to pursue the combination of TTI-621 and nivolumab in an attempt to optimally engage both the innate and adaptive arms of the immune system to generate a robust and enduring anti-tumor response."

On June 7, 2017 Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc. (NASDAQ: SGEN) reported that data from the randomized Phase 3 ALCANZA clinical trial evaluating ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL) were published in the journal Lancet (Press release, Seattle Genetics, JUN 7, 2017, View Source [SID1234519463]). Data were previously presented in an oral session at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 which is expressed on CTCL lesions in approximately 50 percent of patients with the disease. ADCETRIS is currently not approved for the treatment of CTCL.

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!

"Today’s publication of the positive results of the ALCANZA trial is another milestone for our brentuximab vedotin clinical program. We plan to submit the data to regulatory bodies around the world, and if approved, ADCETRIS would be a potential new treatment option for patients with CD30-positive CTCL, a rare, debilitating and often difficult to treat form of cancer," said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. "We are encouraged by the data we’ve seen from our robust ongoing clinical investigation program of ADCETRIS in CD30-positive lymphomas, and are committed to bringing this important therapy to patients."

"The ALCANZA study is the first randomized Phase 3 clinical trial to evaluate a novel agent versus standard of care in CTCL, an incurable and disfiguring disease with few treatment options that achieve durable responses," said Bob Lechleider, M.D., Senior Vice President, Clinical Development of Seattle Genetics. "The data from the ALCANZA trial provide compelling evidence that CTCL patients treated with ADCETRIS had superior outcomes across the primary and all secondary endpoints assessed in the study compared to patients in the control arm who were treated with a standard of care agent. These data demonstrate the potential of ADCETRIS to change the treatment landscape of CTCL."

ALCANZA is a randomized, open-label Phase 3 study designed to evaluate single-agent ADCETRIS versus a control arm of investigator’s choice of the standard of care therapies methotrexate or bexarotene, in patients with CD30-positive CTCL. The manuscript highlights data from the trial which achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.0001). Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the ADCETRIS arm. The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.

Based on the study results, Takeda plans to begin to submit data from the ALCANZA trial to regulatory agencies in its territories in 2017. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to ADCETRIS for the treatment of the most common subtypes of CTCL, mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Seattle Genetics plans to submit these data as part of a supplemental Biologics License Application to the FDA in mid-2017. The ALCANZA trial received a Special Protocol Assessment (SPA) agreement from the FDA and scientific advice from the European Medicines Agency (EMA).

About CTCL

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs. According to published literature, CD30 is expressed on CTCL lesions in approximately 50 percent of patients with the disease.

The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma for which a supplemental BLA is planned in mid-2017.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.

ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

On June 7, 2017 Kura Oncology, Inc. (NASDAQ:KURA), a clinical stage biopharmaceutical company focused on the development of precision medicines for oncology, reported that preliminary data from the ongoing Phase 2 clinical trial evaluating the efficacy, safety and biomarkers of tipifarnib in the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) were selected for a poster presentation at the 14th International Conference on Malignant Lymphoma (ICML) being held June 14-17, 2017 in Lugano, Switzerland (Press release, Kura Oncology, JUN 7, 2017, View Source [SID1234519462]). In addition, Kura’s preliminary Phase 2 data in PTCL were also selected for a poster presentation at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place June 22-25, 2017 in Madrid, 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!

Details for the Poster Presentation at ICML

Title: Preliminary Results from an Open-label, Phase II Study of Tipifarnib in Relapsed or Refractory T-cell Lymphoma
Presenter: Thomas E. Witzig, M.D., Mayo Clinic
Abstract Number: 255
Date and Time: Wednesday, June 14, 2017, poster may be viewed from Wednesday, June 14, 2017 at 12:00 CET through Friday, June 16, 2017 at 18:30 CET
Location: Marquee Parco Ciani

Details for the Poster Presentations at EHA (Free EHA Whitepaper)

Title: Preliminary Results from an Open-label, Phase II Study of Tipifarnib in Relapsed or Refractory T-cell Lymphoma
Presenter: Thomas E. Witzig, M.D., Mayo Clinic
Abstract Number: P571
Poster Session: EHA (Free EHA Whitepaper) 22
Date / Time: Saturday, June 24, 2017, 7:30 – 19:00 CET
Location: IFEMA, Poster Area, Hall 7

In addition, data from a preclinical study of tipfarnib in T-cell leukemia by Dr. Mondejar (IDIVAL, Santander, Spain) showing cell line sensitivity to common T leukemia mutations will be presented at EHA (Free EHA Whitepaper) as an E-poster.

Title: T-Cell Leukemia Sensitivity to Farnesyl Transferase Inhibition Using Tipifarnib
Abstract Number: E834
Date / Time: Friday, June 23, 09:30 CET through Saturday, June 24, 19:30 CET
Location: Poster Area, E-poster screens

On June 7, 2017 Foundation Medicine (NASDAQ: FMI) reported a collaboration with the National Cancer Institute (NCI) and ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) for their precision medicine cancer trial, NCI-Molecular Analysis for Therapy Choice (NCI-MATCH or EAY131) (Press release, Foundation Medicine, JUN 7, 2017, View Source [SID1234519461]). This ongoing study is evaluating the benefit of genomically-guided treatments targeting specific alterations within a person’s tumor, regardless of cancer type. Foundation Medicine will notify physicians at the more than 1,100 clinical sites participating in NCI-MATCH when the comprehensive genomic profiling (CGP) assays they ordered to guide clinical care, FoundationOne or FoundationOne Heme, reveal findings that may make a patient eligible for one of several NCI-MATCH treatments.

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 FoundationOne and FoundationOne Heme assays comprehensively interrogate hundreds of cancer-related genes in solid tumors, or hematologic cancers and advanced sarcomas, respectively, to identify genomic alterations that can help match a patient with a therapy that targets those alterations. Foundation Medicine and its CGP assays were selected for participation in NCI-MATCH based on the validation, reliability and accuracy of the assays, the ability to review a high volume of patient cases due to the mainstream use of FoundationOne and FoundationOne Heme in clinical care today, and the ability to provide assay results in a format that can be uploaded into MATCHbox, the trial’s informatics system that generates patient treatment assignment information for the trial’s panel of experts to review.

"The NCI-MATCH trial is vital to learning more about the genomic basis of cancer biology and the best ways to improve cancer treatment for each individual patient," said Vincent Miller, M.D., chief medical officer at Foundation Medicine. "We believe this innovative trial design leveraging genomics to inform potential treatment modalities will become the standard for oncology clinical studies, particularly to identify signals of effectiveness that can be studied in larger, more definitive trials. We believe our collaboration will help the clinical sites participating in the trial to identify a larger number of patients who may be eligible to enroll for treatment."

Through this collaboration, Foundation Medicine will assist ECOG-ACRIN and the NCI in casting a wider net for patients that may be eligible for NCI-MATCH. Foundation Medicine will identify individuals whose tumors are profiled through standard clinical care with FoundationOne or FoundationOne Heme and are found to harbor genomic alterations being studied in NCI-MATCH, as determined by Foundation Medicine’s proprietary SmartTrials engine that allows for alteration-level specificity in matching patients to the trial. If the individual is identified at a site that is participating in the trial, Foundation Medicine’s SmartTrials outreach services will notify their treating physician that the patient may be eligible for enrollment into NCI-MATCH. The oncologist can take the information into consideration when discussing treatment options with his or her patients. Foundation Medicine initiated inclusion of NCI-MATCH in this outreach in May 2017.

About the NCI-MATCH Study
NCI-MATCH is a phase II precision medicine trial that seeks to determine the effectiveness of treatment that is directed by genomic profiling in patients with solid tumors, lymphomas, or myelomas that have progressed following all standard treatments expected to prolong overall survival or rare cancer types for which there is no standard treatment. The study attempts to demonstrate that matching certain drugs or drug combinations in adults whose tumors have specific gene abnormalities will effectively treat cancer, regardless of its type. Such discoveries could be eligible to move on to larger, more definitive trials.