On June 15, 2017 Portola Pharmaceuticals Inc. (Nasdaq:PTLA) reported the presentation of interim data from a Phase 2a study evaluating cerdulatinib in patients with relapsed/refractory B-cell malignancies (Press release, Portola Pharmaceuticals, JUN 15, 2017, View Source [SID1234519554]). Cerdulatinib is an investigational oral, dual SYK/JAK kinase inhibitor for the treatment of relapsed/refractory B-cell and other hematological malignancies, specifically in patients who have not responded to prior therapies. The data were presented by Paul Hamlin, M.D., chief of the Medical Oncology Service at Memorial Sloan Kettering Basking Ridge during an oral presentation given earlier today at the International Congress on Malignant Lymphoma (ICML) in Lugano, Switzerland.

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The interim results presented at ICML demonstrated evidence of clinical activity in patients with relapsed/refractory (r/r) B-cell malignancies. To date, overall response rates are as follows:

12 out of 18 (67%) partial responses (PRs) in patients with r/r CLL/SLL
5 out of 9 (56%) PRs in patients with r/r FL
1 out of 7 (14%) PRs in patients with other r/r iNHL (marginal zone lymphoma and Waldenstrom macroglobulinemia)
A complete response (CR) was seen in the first r/r peripheral T cell lymphoma (PTCL) patient evaluated in the study
Results also showed that cerdulatinib was generally well-tolerated in these heavily pre-treated patients (at target drug levels). However, three patients at 35 mg BID achieved higher than expected drug concentrations and had severe adverse events (SAEs) including two grade 5 infections and one case of grade three pancreatitis. The dose was subsequently reduced to 30 mg BID and a PK monitoring strategy was implemented. This has resulted in an improved PK and safety profile without compromising clinical activity.

"While we continue to focus our efforts on gaining regulatory approval of our two lead programs, betrixaban and AndexXa (andexanet alfa), we are pleased that our third molecule, cerdulatinib, continues to show promising results in hematologic cancers — an area of great unmet need," said John Curnutte, M.D., Ph.D., executive vice president, research and development of Portola. "We believe these results of our Phase 2a trial further validate cerdulatinib’s potential to control relapsed/refractory B-cell malignancies by a differentiated mechanism of action, inhibiting two key cell signaling pathways that promote cancer. We anticipate an update on the ongoing study and a decision regarding future development by the end of 2017."

"Patients with relapsed/refractory CLL and NHL are difficult to treat and have limited options after failing standard therapy," said Dr. Hamlin. "Presently, there are few effective treatments for patients who have failed prior therapies. The interim results of this clinical trial are very encouraging, and cerdulatinib could represent an important treatment option for these patients if confirmed in further trials."

Additional detail on the interim Phase 2a data will be provided at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) 22nd Annual Congress from June 22-25, 2017.

About the Phase 1/2a Study
The open-label, multicenter, Phase 1/2a proof-of-concept study assessed the safety, pharmacokinetics, pharmacodynamics and clinical activity of oral cerdulatinib in patients with CLL and NHL. In the multi-dose, dose-escalation Phase 1 part of the study, cerdulatinib was administered orally once or twice daily in sequential dose cohorts at increasing dose levels until the maximum tolerated dose was identified. The clinical expansion cohorts in the Phase 2a part of the study are evaluating the safety and efficacy of cerdulatinib in cancer types identified based on results from the dose-escalation phase of the study. Up to 40 patients each will be enrolled in the clinical expansion cohorts including patients with relapsed/refractory chronic lymphocytic leukemia (CLL)/ small lymphocytic leukemia (SLL), and indolent lymphomas such as follicular lymphoma (FL) and peripheral T cell lymphoma (PTCL).

About Cerdulatinib
Cerdulatinib is an oral, dual Syk-JAK inhibitor with a unique mechanism of action. It inhibits two key signaling pathways that promote cancer cell growth in certain hematologic malignancies: the B-cell receptor pathway via Syk and key cytokine receptors via JAK. With its dual pathway mechanism, cerdulatinib may be more effective in specific patients than a single pathway agent, such as those resistant to current therapies or those with known heterogeneous cellular mutations. Preclinical data suggested that cerdulatinib may have anti-tumor activity in patients who did not adequately respond to, or relapsed on, other treatments due to defined mutations.

On June 15, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH), reported results from the dose-escalation part of the ongoing Phase I study of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL), an orphan disease (Press release, Innate Pharma, JUN 15, 2017, View Source [SID1234519552]). IPH4102 is Innate Pharma’s wholly-owned, first-in-class anti-KIR3DL2 humanized therapeutic antibody, designed to trigger immune cell-mediated killing of CTCL cancer cells.

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25 patients, with a median age of 71 years old and a median number of four prior systemic treatments, were evaluable for safety (10 dose levels: 0.0001 to 10 mg/kg). The data from the trial indicate that IPH4102 was well tolerated with no dose-limiting toxicity. The maximum tolerated dose (MTD) was not reached. The majority of adverse events reported was typical for CTCL or reflected low grade infusion-related reactions.

As of May 10, 2017, 24 patients were evaluable for clinical activity. In this population, best global overall response rate (ORR) was 41.7% and disease control rate (DCR) was 91.7% across all dose levels. Best global ORR and DCR reached 47.4% and 89.5% respectively in patients with Sézary syndrome (SS, n=19). Among the 9 patients with SS who achieved clinical responses, one had a global complete response**. 5 complete responses were seen in blood and 2 in skin (resp. 26% and 11%). Median duration of response (DOR) was 8.2 months in all patients and not reached in patients with SS. Median progression free survival (PFS) was 9.0 months in all patients and 10.8 months in patients with SS (range from 0.9 to 17.2). Pruritus was significantly decreased in patients with clinical response.

Pharmacodynamic endpoints and molecular residual disease results are consistent with clinical activity results and show substantial elimination of neoplastic cells in skin and in blood.



Pierre Dodion, Chief Medical Officer of Innate Pharma, commented: "The data reported suggest that IPH4102 is very well tolerated in patients with advanced CTCL and shows promising signs of clinical activity. We are thrilled by these results, given that the trial included patients who had received all available treatment options. They give us confidence for the next steps of the development plan of IPH4102; the cohort expansion part of the trial is planned to start in Q3 2017 at the recommended Phase II dose. We are committed to bringing this potential new therapeutic option to patients and will be focused on working closely with the regulatory authorities during the coming months toward this goal."

Martine Bagot, Principal Investigator and Head of the Dermatology Department at the Saint-Louis Hospital, Paris, added: "We are very pleased with the results of the dose-escalation part of the trial. The profile of IPH4102 is very promising. Today, there is no satisfactory treatment and IPH4102 could be a new therapeutic option for CTCL patients in high medical need at advanced stages of the disease."

These data were presented in an oral presentation at the International Conference on Malignant Lymphoma (ICML) in Lugano on June 14. The presentation is available on the Company’s website

On June 15, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN) and Bristol-Myers Squibb Company (NYSE: BMY) reported an updated interim analysis from the ongoing phase 1/2 clinical trial evaluating ADCETRIS (brentuximab vedotin) and Opdivo (nivolumab) in relapsed or refractory (RR) classical Hodgkin lymphoma (HL) at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (Press release, Bristol-Myers Squibb, JUN 15, 2017, View Source [SID1234519549]). The data reported from 62 patients, including 59 evaluable for response, will be featured in an oral presentation on June 15, 2017. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to help restore anti-tumor immune response. ADCETRIS and Opdivo are not approved in combination for the treatment of RR classical HL or for other indications.

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"The phase 1/2 study combining the antibody-drug conjugate brentuximab vedotin with the PD-1 immune checkpoint inhibitor nivolumab is a promising investigational approach as it combines a targeted therapy with a therapy designed to activate the immune system and the combination may have additive activity," said Alex Herrera, M.D., lead trial investigator and assistant professor at the City of Hope, Duarte, California. "The interim results support further exploration of this novel regimen, free of traditional chemotherapy."

"We are evaluating ADCETRIS in novel combinations in order to identify potential treatment regimens for patients with CD30-expressing lymphomas," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development of Seattle Genetics. "We are pleased to share updated interim results from this ongoing phase 1/2 clinical trial evaluating ADCETRIS in combination with Opdivo in relapsed or refractory HL patients. Since our first patient treated with the combination regimen, the data continue to demonstrate encouraging activity with an acceptable safety profile. These updated data support findings first presented at ASH (Free ASH Whitepaper) 2016. We have nearly doubled the number of patients in our trial evaluating the ADCETRIS/Opdivo combination strategy and recently announced a collaboration with BMS to initiate a pivotal phase 3 clinical trial in relapsed HL patients in mid-2017."

"Bristol-Myers Squibb continues to strengthen our broad Immuno-Oncology and hematology development programs for Opdivo," said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. "Our continued partnership with Seattle Genetics, combines our deep I-O experience and shared commitment to innovative combination treatment options that have the potential to improve the lives of patients impacted by blood cancers. We look forward to further evaluation of ADCETRIS in combination with Opdivo for the treatment of relapsed Hodgkin lymphoma."

Interim Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #074, oral presentation at 6:05 p.m. CEST)

Data were reported from 62 patients with RR classical HL after failure of frontline therapy who received the combination regimen of ADCETRIS plus Opdivo. Patients were treated once every three weeks with up to four cycles of combination therapy. After completion of the fourth cycle of treatment, patients were eligible to undergo an autologous stem cell transplant (ASCT). The median age of patients was 36 years. Forty-five percent of patients had primary refractory disease and 55 percent progressed after responding to frontline therapy, among whom 90 percent received standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine).

Key findings presented include:

Of 59 response-evaluable patients, 50 patients (85 percent) had an objective response, including 37 patients (63 percent) with a complete response and 13 patients (22 percent) with a partial response. Five patients (eight percent) had stable disease and four patients (seven percent) had progressive disease.
Of the 62 patients enrolled, 61 patients (98 percent) received one or more dose of the study therapies. No patients remain on treatment, 58 patients (94 percent) have completed treatment and four patients (six percent) discontinued prior to the end of treatment. At the time of data analysis in the ongoing trial, 37 patients (60 percent) initiated an ASCT and 12 patients (19 percent) received an alternative salvage therapy subsequent to combination therapy. No unusual post-ASCT adverse events were reported. Preliminary analysis shows no impact of ADCETRIS and Opdivo combination on stem cell mobilization or engraftment.
Prior to ASCT, the most common adverse events of any grade occurring in more than 25 percent of patients were nausea (56 percent); fatigue (43 percent); infusion-related reactions (IRRs, 36 percent); pruritus (31 percent); headache (28 percent); and diarrhea, rash and vomiting (all at 26 percent). Treatment-related serious adverse events occurred in five patients (eight percent), including pneumonitis and pyrexia (two patients each) and colitis, malaise, nausea, pneumonia, respiratory failure and sepsis (one patient each).
Infusion related reactions (IRRs) were observed in 41 percent of patients. All IRRs were Grade 3 or less, with the rate of Grade 3 IRRs less than five percent.
ADCETRIS and Opdivo are being evaluated as combination therapy in multiple ongoing clinical trials. In addition to the study presented at ICML, a pivotal phase 3 clinical trial evaluating ADCETRIS in combination with Opdivo compared to ADCETRIS alone in relapsed/refractory HL patients is planned to begin enrollment in mid-2017. In addition, a trial titled "A Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas" is ongoing and focused on patients with relapsed or refractory disease, including diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell, including mediastinal B-cell lymphoma and mediastinal gray zone lymphoma. The companies recently extended the clinical evaluation of ADCETRIS and Opdivo into a clinical trial evaluating the combination as frontline treatment for older HL patients.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system and is the most common type of blood cancer. There are two major categories of lymphoma: HL, also known as Hodgkin disease, and non-Hodgkin lymphoma. HL is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. The disease is most often diagnosed in early adulthood (ages 20-40) and late adulthood (older than 55 years of age). Classical Hodgkin lymphoma is the most common type of HL, accounting for 95 percent of cases. Classical HL is distinguished from other lymphomas by the characteristic presence of CD30-positive Reed-Sternberg cells.

According to the American Cancer Society, more than 8,000 cases of HL will be diagnosed in the United States during 2017 and approximately 1,000 will die from the disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with HL each year and approximately 25,000 people die each year from this cancer. In the European Union, about 12,200 new cases and 2,600 deaths occurred in 2012 as a result of HL.

About ADCETRIS

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-expressing tumor cells.

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. ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory HL and systemic anaplastic large cell lymphoma (sALCL). In addition, 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 Biologics License Application is planned in mid- 2017. See important safety information below.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.