On December 1, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) reported its highlighted data from three ongoing clinical trials evaluating the combination of ADCETRIS (brentuximab vedotin) and Opdivo (nivolumab) at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in San Diego, Calif., December 1-4, 2018 (Press release, Seattle Genetics, DEC 1, 2018, View Source [SID1234531782]). Initial data were presented from a phase 2 clinical trial evaluating the combination in relapsed or refractory primary mediastinal large B-cell lymphoma (PMBL). In addition, data were presented from the ongoing phase 1/2 clinical trial evaluating the combination in relapsed or refractory classical Hodgkin lymphoma (HL). Lastly, an oral presentation on Monday, December 3, 2018 will highlight initial data from a phase 2 study evaluating combination approaches with ADCETRIS, Opdivo and bendamustine in children, adolescents and young adults with relapsed or refractory classical HL. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival. Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to harness the body’s own immune system to help restore anti-tumor immune response. ADCETRIS and Opdivo are not approved in combination for the treatment of relapsed or refractory PMBL, HL or for other indications.

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!

"Our goal with ADCETRIS is to identify the most effective treatment strategies to improve the outcome of patients, and the combination of ADCETRIS and Opdivo has demonstrated enhanced activity with a tolerable safety profile in Hodgkin lymphoma and now a type of non-Hodgkin lymphoma called primary mediastinal large B-cell lymphoma, or PMBL," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "In the Hodgkin lymphoma setting, ADCETRIS plus Opdivo data continue to support investigation of this combination regimen in multiple ongoing studies. The initial data reported from the phase 2 PMBL clinical trial demonstrate a high level of activity of the combination, with an objective response rate of 70 percent and a complete response rate of 27 percent. We and BMS are exploring specific settings where the combination of ADCETRIS and Opdivo has the potential to improve patient outcomes."

Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Preliminary Results from the Phase 2 Checkmate 436 Trial (Abstract #1691, poster presentation on Saturday, December 1, 2018)

Data from the Checkmate 436 phase 2 trial of 30 patients with relapsed or refractory PMBL who received a combination of ADCETRIS plus Opdivo treatment after failure of frontline therapy or autologous stem cell transplant (ASCT) will be presented for the first time. Patients were treated once every three weeks until disease progression or unacceptable toxicity. The median age of patients was 35.5 years. Key findings will be presented in a poster presentation by Alison Moskowitz, M.D., Clinical Director, Lymphoma Inpatient Unit, Memorial Sloan Kettering Cancer Center, New York, and include:

Of 30 response-evaluable patients, 21 patients (70 percent) had an objective response, including eight patients (27 percent) with a complete response and 13 patients (43 percent) with a partial response, three patients (10 percent) with stable disease, four patients (13 percent) with progressive disease and two patients (seven percent) unable to determine.
Median time to response was 1.3 months and time to complete response was 3 months. Median duration of response and duration of complete response were not reached.
The most common adverse events (AEs) of any grade in at least 20 percent of patients were neutropenia (27 percent) and peripheral neuropathy (20 percent). The most common Grade 3 or 4 AEs were neutropenia (27 percent); thrombocytopenia and decreased neutrophil count (seven percent each); and hypersensitivity, diarrhea and maculopapular rash (all three percent). Immune-mediated AEs included diarrhea, maculopapular rash and hyperthyroidism.
Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Classic Hodgkin Lymphoma: Part 3 (Concurrent Dosing) Results and Updated Progression-Free Survival Results from Parts 1 and 2 (Staggered Dosing) (Abstract #1635, poster presentation on Saturday, December 1, 2018)

Data will be reported from 30 patients with relapsed or refractory HL who received concurrent combination of ADCETRIS plus Opdivo treatment after failure of frontline therapy, representing Part 3 of the study. Patients were treated once every three weeks, with up to four cycles of combination therapy in the outpatient setting. After completion of the fourth cycle of treatment, patients were eligible to undergo an ASCT. The median age of patients was 31.5 years. Data from Parts 1 and 2 of the study were recently reported at the 11th International Symposium on Hodgkin Lymphoma (ISHL) and can be found here. Key findings will be presented in a poster presentation and include:

Of 30 response-evaluable patients, 28 patients (93 percent) had an objective response, including 24 patients (80 percent) with a complete response and four patients (13 percent) with a partial response, one patient each (three percent) with stable and progressive disease.
After a median follow-up time of 12.7 months, the estimated PFS at 12 months was 89 percent.
The most common AEs of any grade occurring prior to ASCT or subsequent salvage therapy in at least 15 percent of patients were nausea (57 percent), diarrhea and fatigue (37 percent each), vomiting (33 percent), infusion-related reaction (IRR; 30 percent), headache (27 percent), pruritus and pyrexia (23 percent each), and abdominal pain and chills (20 percent each). The majority of IRR AE symptoms were Grade 2 or less and included no treatment discontinuations.
An additional poster will be presented on Monday, December 3, 2018 from the phase 1/2 clinical trial evaluating ADCETRIS in combination with Opdivo in relapsed or refractory HL titled "Baseline Tumor Transcriptome Characteristics Associated with the Response of Relapsed/Refractory Hodgkin Lymphoma Patients to Brentuximab Vedotin in Combination with Nivolumab" (Abstract #2837).

Additional ADCETRIS and Opdivo ASH (Free ASH Whitepaper) Data Presentation

The first data will be reported in an oral presentation from the phase 2 CheckMate-744 study, the first risk-stratified, response-adapted study of ADCETRIS and Opdivo, followed by ADCETRIS and bendamustine for suboptimal response, in children, adolescents and young adults with relapsed/refractory classical HL, prior to ASCT. At time of analysis, all evaluable patients achieved complete metabolic remission after completing induction and, as needed, intensification therapy. The most common AEs were nausea (53 percent), diarrhea (31 percent) and pyrexia (28 percent). No AEs led to discontinuation and there were no deaths. Presentation information includes:

Response-Adapted Therapy with Nivolumab and Brentuximab Vedotin (BV), Followed by BV and Bendamustine for Suboptimal Response, in Children, Adolescents and Young Adults with Standard Risk Relapsed/Refractory Classical Hodgkin Lymphoma (Abstract #927, oral presentation on Monday, December 3, 2018 at 5:00 p.m. PT at the San Diego Convention Center, Room 6F)
About ADCETRIS (brentuximab vedotin)

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three recently completed phase 3 trials: ECHELON-2 in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma. The phase 3 CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma is ongoing.

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.

ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, 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 December 1, 2018 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported preclinical data presented at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting demonstrating that voruciclib, MEI’s orally available CDK9 inhibitor, synergistically induced apoptosis at clinically relevant concentrations when combined with venetoclax (marketed as Venclexta) in human derived acute myeloid leukemia (AML) cells lines and patient samples (Press release, MEI Pharma, DEC 1, 2018, View Source [SID1234531766]). Voruciclib is currently being evaluated in a Phase 1b dose ranging study in patients with B-cell malignancies.

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 data presented today demonstrate the synergistic induction of apoptosis of voruciclib when combined with venetoclax via the transient downregulation of MCL1 in multiple AML cell lines and patient samples. Inhibition of CDK9 blocks the production of MCL1, which is an established resistance mechanism to the BCL-2 inhibitor venetoclax.

"This study evaluating the synergistic activity of voruciclib in AML cells builds on existing preclinical data demonstrating similar activity in other B-cell malignancies, including diffuse large B-cell lymphoma and chronic lymphocytic leukemia, and reinforces the significant clinical utility voruciclib may hold when combined with inhibitors of BCL-2 in B-cell disease," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "As we progress in our ongoing Phase 1 study, we look forward to selecting the voruciclib clinical dose to evaluate in combination with venetoclax to clinically assess synergies and the opportunity for combination treatments across multiple indications."

The voruciclib ASH (Free ASH Whitepaper) 2018 poster can be accessed on the MEI Pharma website.

About Voruciclib
The CDK family of proteins are important cell cycle regulators. CDK9 is a transcriptional regulator of the myeloid leukemia cell differentiation protein ("MCL1"), a member of the family of anti-apoptotic proteins which, when elevated, may prevent the cell from undergoing cell death. Inhibition of CDK9 blocks the production of MCL1, which is an established resistance mechanism to the B-cell lymphoma ("BCL-2") inhibitor venetoclax.

CDK9 is also a transcriptional regulator of MYC, a transcription factor regulating cell proliferation and growth which contributes to many human cancers and is frequently associated with poor prognosis and unfavorable patient survival. Targeting MYC directly has historically been difficult, but CDK9 is a transcriptional regulator of MYC and is a promising approach to target this oncogene.

In August 2018 MEI dosed the first patient in a dose ranging Phase 1b clinical trial of voruciclib as a single agent in patients with relapsed and/or refractory B-cell malignancies after failure of prior standard therapies to determine the safety, preliminary efficacy and maximum tolerated dose. We also plan to evaluate voruciclib in combination with venetoclax to assess synergies and the opportunity for combination treatments across multiple indications.

On December 1, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported the presentation of clinical data from two ongoing trials of its investigational Bruton’s tyrosine kinase (BTK) inhibitor, zanubrutinib, in patients with mantle cell lymphoma (MCL) (Press release, BeiGene, DEC 1, 2018, View Source;p=irol-newsArticle&ID=2378923 [SID1234531783]). The presentations were made at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), taking place December 1-4, 2018 in San Diego, CA.

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!

Results from the pivotal Phase 2 trial of zanubrutinib in Chinese patients with relapsed or refractory (R/R) MCL (ClinicalTrials.gov Identifier: NCT03206970) were featured in an oral presentation, while updated results from the global Phase 1 trial of zanubrutinib in patients with multiple subtypes of B-cell malignancies, including treatment naïve (TN) and R/R MCL (ClinicalTrials.gov Identifier: NCT02343120), were featured in a poster presentation.

"Taken together, we believe that these two studies provide encouraging evidence for the use of zanubrutinib as a potential therapy in patients with MCL," said Jane Huang, M.D., Chief Medical Officer, Hematology, at BeiGene. "The results from 86 patients enrolled in our pivotal Phase 2 study in Chinese patients with R/R MCL presented today at ASH (Free ASH Whitepaper), provide a thorough look into the data included in our first new drug application (NDA) in China for zanubrutinib. Additionally, the results from 48 patients with MCL enrolled in our global Phase 1 study illustrated consistent outcomes for patients studied outside of China. We are excited by the prospect that zanubrutinib may be a differentiated BTK inhibitor with deep, durable responses for patients with MCL and potentially for other B-cell malignancies."

Zanubrutinib was discovered by BeiGene scientists, and is being developed globally as a monotherapy and in combination with other therapies to treat various hematologic malignancies. Zanubrutinib is being studied in several clinical trials as part of a broad development program and was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with Waldenström macroglobulinemia (WM). BeiGene plans to submit an initial NDA to the FDA for zanubrutinib in 2019 or early 2020. The NDAs in China for R/R MCL and R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) have been accepted by the National Medical Products Administration (NMPA, formerly known as CFDA) and the MCL filing has been granted priority review.

"Zanubrutinib was shown to be highly active in Chinese patients with R/R MCL, as evidenced by a high rate of complete responses characterized by PET-based imaging. It was also generally well-tolerated, and we are hopeful of its potential to become a new treatment option for Chinese patients with MCL and potentially other forms of B-cell lymphomas," said Yuqin Song, M.D., Ph.D., Associate Professor of Medical Oncology, Deputy Director of the Lymphoma Department at Peking University Cancer Hospital in China, and presenter of results from the pivotal Phase 2 trial in Chinese patients.

"The outcomes observed in patients treated outside of China are generally consistent with the experiences observed in Chinese patients with R/R MCL. Importantly, the high response rates that were observed appear to extend to patients with both TN and R/R MCL," commented Constantine Tam, M.D., Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at Peter MacCallum Cancer Center and Director of Hematology at St. Vincent’s Hospital, Australia, and lead author of the poster presentation of results from the global Phase 1 trial.

Summary of Clinical Results From the Pivotal Phase 2 Trial in China
Oral Presentation Data Included in BeiGene’s NDA in China for Zanubrutinib in MCL

This single arm, open-label, multi-center, pivotal Phase 2 trial of zanubrutinib as a monotherapy in Chinese patients with R/R MCL enrolled 86 patients who had received a median of two prior lines of therapy (1-4). Patients were treated with zanubrutinib, dosed at 160 mg orally twice-daily (BID). The primary endpoint of the trial was overall response rate (ORR) assessed by independent review committee (IRC) using PET-based imaging according to the Lugano Classification 2014.

As of March 27, 2018, 85 patients with R/R MCL were evaluable for efficacy and 65 patients (75.6%) remained on study treatment. The median follow-up time for patients enrolled in the trial was 35.9 weeks (1.1-55.9). Results included:

The ORR by IRC was 83.5 percent (71/85); the complete response (CR) rate was 58.8 percent (50/85) and the partial response (PR) rate was 24.7 percent (21/85);

The 24-week progression-free survival (PFS) was estimated at 82 percent. The median PFS had not yet been reached;

With 24.1 weeks median follow-up (0.1-41.1), the median duration of response (DOR) had not yet been reached and 90 percent of responders were still in response at 24 weeks;

Zanubrutinib tolerability was generally consistent with previous reports in patients with various B-cell malignancies and the majority of adverse events (AEs) were grade 1 or 2 in severity. The most frequent AEs of any attribution were neutrophil count decreased (31.4%), rash (29.1%), upper respiratory tract infection (29.1%), and platelet count decreased (22.1%);

The most frequently reported (in >5 percent of patients) grade 3 or higher AEs were neutrophil count decreased (11.6%) and lung infection (5.8%);

Four patients (4.7%) had treatment emergent adverse events (TEAEs) leading to death (one case each of traffic accident, cerebral hemorrhage, pneumonia, and unknown cause in the setting of infection); and

Among events of special interest for BTK inhibitors, diarrhea was observed in nine patients (10.5%), all grade 1-2. Major hemorrhage was observed in 1 patient (1.2%) with blastoid variant of MCL who had intra-parenchymal CNS bleeding. No cases of atrial fibrillation/flutter were reported in this trial.
Summary of Updated Clinical Results From the Global Phase 1 Trial

This open-label Phase 1 trial of zanubrutinib as a monotherapy in patients with different subtypes of B-cell malignancies, including MCL, is being conducted in Australia, New Zealand, the United States, Italy, and South Korea. As of July 24, 2018, 48 patients with TN (n=9) or R/R (n=39) MCL have been enrolled in the trial and the median follow-up time was 12.7 months (0.7-38.0). Forty-five patients including six with TN and 39 with R/R MCL, were evaluable for efficacy in this analysis, per the Lugano 2014 classification. At the time of the data cutoff, 26 patients remained on study treatment. Updated results included:

The ORR by investigator was 88.9 percent (40/45); the CR rate was 26.7 percent (12/45) and the PR rate was 62.2 percent (28/45). The majority of patients were assessed via CT-scan; PET scans were optional per trial protocol;

The median DOR was 16.2 months and the median PFS for R/R patients was 18.0 months (0.7-30.7);

Zanubrutinib tolerability was generally consistent with previous reports in patients with various B-cell malignancies and the majority of AEs were grade 1 or 2 in severity. The most frequent AEs of any attribution were petechia/purpura/contusion (33.3%), diarrhea (33.3%), upper respiratory tract infection (29.2%), fatigue (25.0%), and constipation (18.8%);

Grade 3-5 AEs occurred in 56.3 percent of patients. Grade 3-5 AEs of any attribution reported in > three patients included anemia (8.3%), major hemorrhage (6.3%), cellulitis (6.3%), myalgia (6.3%), neutropenia (6.3%), pneumonia (6.3%); and thrombocytopenia (6.3%);

Discontinuation due to AEs occurred in 18.8 percent of patients with all but one event (peripheral edema) determined to be unrelated to study drug; and

There were four deaths due to AEs, which were all determined by the investigators to be unrelated to zanubrutinib treatment.
Investor Webcast

Date and Time: Monday, December 3, 2018 at 20:00 PST (Tuesday, December 4 at 12:00 China Standard Time)
Webcast: A live webcast and replay of the event will be available on BeiGene’s investor website, View Source
About Mantle Cell Lymphoma
Lymphoma is a diverse group of malignancies that originates from B-, T- or NK- cells. Mantle cell lymphoma (MCL) is typically an aggressive form of non-Hodgkin lymphoma (NHL) that arises from B-cells originating in the "mantle zone." In 2013, the incidence of lymphoma was 4.2 per 100,000 and the mortality was 2.2 per 100,000 in mainland Chinai, making it the eleventh most common cancer and the tenth leading cause of cancer death.ii In the United States, about 70,800 new cases of NHL were expected in 2014, with MCL representing about six percent (about 4,200 cases) of all new cases of NHL in the United Statesiii. Mantle cell lymphoma usually has a poor prognosis, with a median survival of three to four years, although occasionally patients may have an indolent course.iv Frequently, mantle cell lymphoma is diagnosed at a later stage of disease.

About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that is currently being evaluated in a broad pivotal clinical program globally as a monotherapy and in combination with other therapies to treat various B-cell malignancies.

Clinical trials of zanubrutinib include a global Phase 1 trial; a fully-enrolled, global Phase 3 clinical trial in patients with Waldenström macroglobulinemia (WM) comparing zanubrutinib to ibrutinib, the currently approved BTK inhibitor for WM; a global Phase 3 clinical trial in patients with previously untreated chronic lymphocytic leukemia (CLL); a pivotal Phase 2 trial in patients with relapsed/refractory (R/R) follicular lymphoma in combination with GAZYVA (obinutuzumab); and a Phase 3 trial comparing zanubrutinib to ibrutinib in patients with R/R CLL/small lymphocytic lymphoma (SLL). In China, BeiGene has completed enrollment in two other pivotal Phase 2 clinical trials of zanubrutinib in patients with CLL/SLL and WM. New drug applications (NDA) for zanubrutinib in patients with R/R MCL and in patients with R/R CLL/SLL have been accepted by the National Medical Products Administration (NMPA, formerly known as CFDA) and the MCL filing has been granted priority review.

On December 1, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported late interim results from its BP-004 European registration trial, suggesting that adding rivo-celTM (rivogenlecleucel, formerly BPX-501) to stem cell transplants in patients who lack a matched donor may deliver comparable outcomes to matched unrelated donor (MUD) transplants (Press release, Bellicum Pharmaceuticals, DEC 1, 2018, View Source [SID1234531767]). The data were reviewed in a presentation today at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2018) by Mattia Algeri, M.D., Cell and Gene Therapy Unit, Ospedale Bambino Gesù, Rome, Lazio, Italy.

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 interim data show a 90.9 percent event-free survival (EFS) rate at 180 days for patients treated with rivo-cel (n=166) after a stem cell transplant from a haploidentical, or partially matched, donor. These results appear comparable to an interim evaluation of patients who received a MUD transplant in the concurrently-run observational study (n=91), demonstrating an 87.7 percent EFS rate at 180 days. The Company expects to report final comparison results from both study populations and file for approval in Europe in 2019. Demonstrating non-inferiority to MUD transplantation is the primary study objective required for rivo-cel product registration in Europe.

"While a stem cell transplant is an established, often curative treatment option for children with cancers and hereditary blood diseases, the majority of patients are unable to find an HLA-matched related donor, which is associated with the best outcomes," commented Dr. Algeri. "While matched unrelated donor transplants are an important option, only half of patients can identify a match. Further, it can take up to several months to do so, a delay that is problematic for many transplant patients. These data suggest that rivo-cel treatment may enable haploidentical stem cell transplant with overall outcomes similar to MUD, making it an attractive alternative for many of these patients."

Study Design and Highlights

The BP-004 trial is a prospective, multicenter, European Phase 1/2 trial in pediatric patients with malignant or nonmalignant disorders. Patients received rivo-cel within a few weeks following a haplo-transplant. No post-transplant Graft versus Host Disease (GvHD) prophylaxis was used. Patients who developed visceral GvHD or were refractory to standard of care treatments were eligible to receive rimiducid. The primary endpoint was EFS at day 180 (events included transplant-related mortality or non-relapse mortality for malignant patients, severe GvHD, and life-threatening infections).

Rivo-cel was well-tolerated, with few patients experiencing non-GvHD adverse events considered to be possibly or probably related to rivo-cel. Overall GvHD rates were low, with few cases of high-grade acute GvHD or chronic GvHD. The majority of patients with visceral GvHD or who were refractory to standard of care treatment for GvHD responded to rimiducid.

The observational comparator trial (C/CP-004) was designed to collect both prospective and retrospective data from pediatric patients with either malignant or nonmalignant disease who underwent a matched unrelated donor transplant during the same time period and at the same treatment centers where the BP-004 rivo-cel study was conducted.

"These interim data increase our confidence that rivo-cel may be an approvable new treatment option for transplant patients with leukemias, lymphomas and genetic blood diseases in Europe upon final data read-out in 2019," commented Rick Fair, Bellicum President & CEO. "If we continue to demonstrate that rivo-cel enables patients without a matched donor to achieve outcomes comparable to a MUD transplant, that would be very clinically meaningful and would fulfill a requirement for European approval. We look forward to reporting final six-month results for all patients in 2019. We also plan to continue to follow these patients to evaluate the impact of rivo-cel in preventing relapse and extending overall survival, particularly in patients with leukemia."

A copy of this ASH (Free ASH Whitepaper) presentation will be made available in the Abstracts & Presentations section of the Company’s website. The Company expects to report topline final results in early 2019 followed by publication of a comprehensive data set.

Analyst and Investor Luncheon Event and Webcast
Bellicum will host a live and webcast analyst and investor luncheon event on December 3, 2018 at 12:00 p.m. – 1:30 p.m. PST in San Diego, CA. Featured speakers include Dr. Alice Bertaina, Associate Professor of Pediatrics (Stem Cell Transplantation), Lucile Packard Children’s Hospital at the Stanford School of Medicine, as well as Bellicum senior management. A webcast replay of the event will be available in the News & Events section of the Bellicum website, and available for at least two weeks following the event.

About Rivo-cel (BPX-501)
Rivo-celTM (rivogenlecleucel) is an allogeneic polyclonal T cell product designed to reduce relapse of leukemia following a stem cell transplant. The cell treatment contains a diverse repertoire of T cells which may contribute to a robust graft vs. leukemia effect. Rivo-cel’s antiviral benefits may also reduce morbidity and mortality in patients susceptible to infection following a transplant. The product’s CaspaCIDe safety switch enables this approach by allowing physicians to reduce the number of alloreactive cells in the event of uncontrolled GvHD. Rivo-cel addresses a major unmet need in adult and pediatric leukemia, lymphoma and genetic blood disease patients following a haploidentical stem cell transplant.

On December 1, 2018 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported a presentation of the first interim data with melflufen (Ygalo) from the ongoing phase I/II study ANCHOR at the 60th ASH (Free ASH Whitepaper) meeting in San Diego, California, USA (Press release, Oncopeptides, DEC 1, 2018, View Source [SID1234531802]).

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!

Overall conclusions

The combinations of melflufen and dexamethasone (dex) with either bortezomib or daratumumab in relapsed-refractory multiple myeloma (RRMM) patients are well tolerated
No dose limiting toxicity has been observed at the melflufen 30 and 40 mg dose levels in either regimens. The 40 mg dose level is still recruiting patients
An Overall Response Rate (ORR) of 86% was observed with melflufen and dexamethasone in combination with daratumumab (CD38-directed monoclonal antibody)
An Overall Response Rate (ORR) of 100% was observed with melflufen and dexamethasone in combination with bortezomib (proteasome inhibitor)
The data are presented in a poster that can be found at: www.oncopeptides.com / presentations / 60th ASH (Free ASH Whitepaper)

CEO comments

"Although, these are early data and small patient samples, it is encouraging to see that melflufen is well tolerated and has a very high level of activity with no cross resistant pattern in combination regimens. These patients have undergone 2-3 prior lines of therapy and have developed resistant disease. The interim data show a very good efficacy profile for melflufen in combination with either bortezomib or daratumumab. In a cross-study comparison in RRMM patients treated with combination regimens our interim data with an ORR in the range 86-100% stand out positively. The treatment landscape changes over time and there is a high need of new treatment options with a novel mechanism of action like melflufen" said Jakob Lindberg, CEO of Oncopeptides.

About the ANCHOR study

The study recruitment is ongoing. ANCHOR is a phase I/II study where melflufen and dexamethasone (dex) is dosed in combination with either bortezomib or daratumumab. All patients must have 1-4 prior lines of therapy and be refractory (or intolerant) to an immunomodulary agent (IMiD) or a proteasome inhibitor (PI) or both.

In combination with bortezomib (Regimen A) patients cannot be refractory to a PI and in combination with daratumumab (Regimen B) patients cannot be previously exposed to any anti-CD38. Patients will be treated until documented disease progression or unacceptable toxicity. The primary objective of the phase I part of the study is to determine the optimal dose of melflufen and dex, up to a maximum of 40 mg, in combination with bortezomib or daratumumab. An additional 20 patients per regimen will be recruited in the phase II part of the study where the primary objective is ORR.

Summary of the ANCHOR interim data

Melflufen in combination with bortezomib – Regimen A

At the time of the data cut-off November 12, 2018, 3 patients had been treated with 30 mg melflufen and dex in combination with bortezomib. Median age was 81 years with a median of 3 prior lines of therapy. All patients were relapsed-refractory and 2 out of 3 patients were last line refractory (disease progression while on therapy). All patients were ongoing at the time of the data cut-off with a median treatment duration of 5.8 months.

The patients received a total of 17 cycles of treatment with a median of 7. All 3 patients achieved partial response (PR). No dose limiting toxicities were observed at the 30 mg melflufen dose level and the melflufen 40 mg has been opened for enrollment. The regimen was well tolerated with clinically manageable G3/4 hematological AEs and the low number of non-hematological AEs was noteworthy.

Melflufen in combination with daratumumab – Regimen B

At the time of the data cut-off, November 12, 2018, 9 patients had been treated with melflufen in combination with daratumumab and dex. Median age was 63 years with a median of 2 prior lines of therapy. No patient had achieved CR in any previous line of therapy, 67% were IMiD refractory and 56% were last line refractory (disease progression while on therapy). All patients were ongoing at the time of the data cut-off.

All 9 patients were still ongoing with a median treatment duration of 3.9 months. They received a total of 39 cycles of treatment with a median of 4.

Overall response rate N/A*
ORR CR VGPR PR MR SD PD
total, N=9 86% 0 4 2 0 1 0 2
*2 of the 9 patients were still in their first cycle of treatment and were therefore not evaluable for response as described at time for data cut.

4 patients were treated with 30 mg melflufen and 5 patients were treated with 40 mg melflufen with no dose limiting toxicity observed. The combination of melflufen, dexamethasone and daratumumab was well tolerated with clinically manageable G3/4 hematological AEs and the low number of non-hematological AEs was noteworthy.

About Melflufen

Melflufen (Ygalo), a peptide conjugated alkylator belonging to a novel class of peptidase-enhanced compounds, targets multiple myeloma (MM) cells with a unique mechanism of action. Aminopeptidases are enzymes found in all cells but are over-expressed in several cancers including MM. Ygalo selectively targets MM cells through aminopeptidase-driven accumulation. In vitro experiments show a 50-fold enrichment of the active substance in MM cells compared with administration of equal amount of an alkylator not enriched by aminopeptidases. The enrichment results in selective cytotoxicity (increased on-target potency and decreased off-target toxicity), and that resistance pathways of existing myeloma treatments (including alkylators) is overcome. Melflufen also demonstrates strong anti-angiogenic properties.

Melflufen in clinical development

Melflufen (Ygalo) has been used to treat late-stage RRMM patients in both phase I and phase II clinical studies (O-12-M1) with favorable results. Currently, melflufen is being studied in four clinical trials for the treatment of multiple myeloma. The current studies are OCEAN, HORIZON, ANCHOR and BRIDGE.

The current clinical study program is intended to demonstrate better results from treatment with melflufen compared to established alternative drugs for patients with multiple myeloma. Melflufen could potentially provide physicians with a new treatment option for patients suffering from this serious disease.

Melflufen has been investigated in the treatment of late-stage relapsed refractory multiple myeloma (RRMM) patients. This was done in the clinical study O-12-M1 where strong final results were reported in December 2017. Currently, four clinical studies are ongoing with melflufen.

OCEAN is Oncopeptides pivotal Phase III study where melflufen is compared directly with current standard of care, pomalidomide, in late-stage RRMM patients.

HORIZON is a Phase II study that studies the effect of melflufen in late-stage RRMM patients with few or no remaining established treatment options. Updated interim data from this study will be presented at ASH (Free ASH Whitepaper) in December 2018.

ANCHOR is a phase I/II study where melflufen is administered in combination with either bortezomib or daratumumab in RRMM patients. The results of this study aim to create understanding and knowledge among treating physicians for how melflufen can be used in combination with these drugs. In addition, the results could open up for the use of melflufen in earlier lines of treatment.

BRIDGE is a phase II study, where melflufen is used in RRMM patients with impaired renal function. This is a positioning study to show melflufen’s treatment profile in these patients.