MorphoSys Presents Updated Clinical Data for Anti-CD38 Antibody MOR202 in Multiple Myeloma at EHA 2018

On June 15, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; Nasdaq: MOR) reported its updated data from the ongoing phase 1/2a study of the anti-CD38 antibody MOR202 in relapsed/refractory multiple myeloma at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting 2018 in Stockholm (Press release, MorphoSys, JUN 15, 2018, View Source [SID1234527339]). The dose escalation trial comprises three arms: MOR202, MOR202 in combination with the immunomodulatory drug (IMiD) lenalidomide (LEN), and MOR202 in combination with the IMiD pomalidomide (POM), in each case with low-dose dexamethasone (DEX).

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"We are optimistic about the responses seen in patients with multiple myeloma treated with MOR202 plus LEN/DEX and POM/DEX based on matured data as well as about the low proportion of patients experiencing infusion-related reactions," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "There is a medical need for new treatment options in multiple myeloma and we look forward to further maturing data from this ongoing trial."

In total, 56 patients were evaluable for safety and efficacy analysis in the clinically relevant dose cohorts of MOR202 (4 mg/kg, 8 mg/kg, 16 mg/kg) by the time of the data cut-off at December 31, 2017. At data cut-off, 16 patients remained in the study. Of the 56 evaluable patients, 18 had received MOR202 plus DEX, 21 received the combination of MOR202 and POM/DEX and 17 received MOR202 plus LEN/DEX.

MOR202 was given as a two-hour infusion up to the highest dose of 16 mg/kg. Infusion-related reactions (IRRs) occurred in 11% of patients in the clinically relevant dose cohorts of MOR202 and were limited to grade 1 or 2. Further, infusion time could be shortened to 30 minutes in the majority of the 16 patients remaining on study as per the data cut-off date.

The most frequent adverse events of grade 3 or higher were neutropenia, lymphopenia, and leukopenia in 52%, 48%, and 39% of patients, respectively. No unexpected safety signals were observed.

Patients treated with MOR202 in combination with LEN/DEX had a median of two prior treatment lines, 59% being refractory to at least one prior therapy. Median progression-free survival (PFS) was not yet reached. With six of the 17 patients in this cohort still on study at data cut-off, the median follow-up was 16.6 months. An objective response was observed in eleven out of 17 patients (65%), with two complete responses (CR), three very good partial responses (VGPR) and seven partial responses (PR).

Patients receiving MOR202 with POM/DEX, had a median of three prior treatment lines, all being refractory to the last prior therapy. Median PFS was 17.5 months. With ten out of 21 patients in this cohort still on study at data cut-off, the median follow-up was 6.5 months. An objective response was observed in ten out of 21 patients (48%), with two patients achieving a complete response (CR), four patients with a very good partial response (VGPR) and four partial responses (PR).

Patients treated with MOR202 plus DEX had a median of three prior treatment regimens, with 67% being refractory to any prior therapy. Median PFS in this cohort was 8.4 months. All patients had discontinued the study before data cut-off, i.e., follow-up for this cohort is completed. An objective response was observed in five out of 18 patients (28%).

Details of the MOR202 presentation at EHA (Free EHA Whitepaper) 2018

Abstract Code: S848

MOR202 with low-dose dexamethasone (DEX) or pomalidomide/DEX or lenalidomide/DEX in relapsed or refractory multiple myeloma (r/r MM): A phase I/IIa, multicenter, dose-escalation study

The oral presentation will be given during the session "New therapeutic strategies to improve the outcome of relapse/refractory plasma cell disorders" on Saturday, June 16, 2018, from 4:15-4:30pm CEST (10:15-10:30am EDT), in Room A1 at the Stockholmsmässan in Stockholm.

Additional information can be found at www.ehaweb.org, including the abstracts.

MorphoSys Presents Clinical Data with Blood Cancer Candidate MOR208 in Chronic Lymphocytic Leukemia at EHA 2018 Conference

On June 15, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment; TecDAX; Nasdaq: MOR) reported the presentation of clinical data from the exploratory phase 2 COSMOS trial (Press release, MorphoSys, JUN 15, 2018, View Source [SID1234527338]). The trial evaluates MorphoSys’s proprietary hemato-oncological drug candidate MOR208 in combination with the cancer drug idelalisib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), who progressed on or were intolerant to ibrutinib therapy. Data will be presented in a poster presentation on June 15, 2018, at the 23rd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Stockholm/Sweden. MOR208 is an investigational Fc-enhanced humanized monoclonal antibody directed against CD19 in clinical development for the treatment of B cell malignancies.

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"Patients with CLL after failure of ibrutinib therapy are in need of more therapeutic options. We are encouraged by the initial and, for the most part, still ongoing responses observed in this heavily pretreated patient population in our exploratory trial with MOR208 plus idelalisib," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "Overall, this shows the potential medical application of MOR208 in additional B cell malignancies. The data shows that MOR208 may be combined with other cancer drugs used in hematological malignancies, including PI3K inhibitors. We look forward to the upcoming results from the second cohort of MOR208 plus venetoclax of our ongoing COSMOS study which we expect later this year."

COSMOS is a phase 2, two-cohort, open-label, multicenter study evaluating the preliminary safety and efficacy of MOR208 combined with idelalisib (cohort A) or venetoclax (cohort B) in patients with r/r CLL/SLL previously treated with Bruton’s Tyrosine Kinase inhibitor (BTKi) ibrutinib.

Data presented at EHA (Free EHA Whitepaper) 2018 comprise preliminary safety and efficacy data on all 11 patients enrolled into cohort A (cut-off date: January 29, 2018). Patients enrolled had received a median of five prior treatment lines (range: 2-9 prior lines). Nine out of the eleven patients enrolled (82%) had discontinued prior ibrutinib treatment due to progressive disease and two patients (18%) due to toxicity.

The most common treatment-emerging adverse events (TEAEs) of grade 3 or higher were hematologic, with neutropenia observed for four patients (36%) and anemia for three patients (27%) being the most common reported events. Ten treatment-emergent serious adverse events (SAEs) were reported in five patients (45%) none of them being fatal. All except one of the six treatment-related SAEs reported for three patients (27%) were suspected to idelalisib.

According to the preliminary efficacy analysis conducted by the investigators, overall response rate (ORR) was 82%, including one complete response (CR, 9%) confirmed by bone marrow biopsy and eight partial responses (PR, 73%). In addition, two patients (18%) showed stable disease. The median observation time was 4.2 months. At the time of data-cut off, six patients continued treatment. One patient with a very good partial response according to response criteria was taken off the study to receive stem cell transplantation. Two previously responding patients had to discontinue the study due to progressive disease. Two patients (one PR, one stable disease SD) discontinued due to adverse events.

Details about the poster presentation on MOR208 at EHA (Free EHA Whitepaper) 2018:

Abstract Code: PF350

Two-cohort, phase II study in R/R CLL (COSMOS): First preliminary safety and efficacy results of MOR208 treatment in combination with idelalisib in patients who discontinued prior ibrutinib therapy

The poster will be presented during the session "Chronic lymphocytic leukemia and related disorders – Clinical" on Friday, June 15, 2018 5:30-7:00 pm CEST (11:30am-1:00pm EDT), in the poster area at the Stockholmsmässan in Stockholm.

In addition, the corresponding abstract will be on display on the E-poster screens at the conference from Friday, June 15, 2018, 9:30 am CEST (3:30 am EDT) to Sunday, June 17, 2018, 1:00 pm CEST (7:00 am EDT).

Additional information can be found at www.ehaweb.org, including the abstract.

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) is investigating the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the FDA granted Breakthrough Therapy Designation for MOR208 plus lenalidomide in this patient population. The pivotal phase 2/3 B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. In addition, MOR208 is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.

Molecular Partners presents updated results from its ongoing Phase 2 combination study of its lead oncology drug MP0250 at EHA in Stockholm

On June 15, 2018 Molecular Partners AG (SIX: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported that the company will present updated preliminary results from the ongoing Phase 2 study of its lead proprietary oncology drug MP0250 at the 23th Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm (Press release, Molecular Partners, JUN 15, 2018, View Source [SID1234527337]).

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The ongoing, open label Phase 2 clinical study[1] is examining the safety and efficacy of MP0250 in combination with bortezomib (Velcade) and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) who have failed at least two lines of standard therapies, including bortezomib and an IMiD. The study is being performed at nine centers in Germany, Poland and Italy.

In the first of two cohorts, patients received MP0250 at 8mg/kg every 3 weeks (corresponding to 66% of the recommended dose) in combination with standard doses of bortezomib and dexamethasone.

All patients had been pretreated with at least two lines of therapy, including an IMiD and bortezomib. 50% of those patients were considered proteasome refractory. At the data cutoff on May 21, 2018, five of eight evaluable patients achieved an objective response (4 patients with PR/partial response; 1 patient with VGPR/very good partial response). Responses were durable, with median time on treatment for responding patients of 22.5 weeks and the longest response still ongoing at 41 weeks.

Main adverse events were consistent with the known side effect profile of VEGF-targeting agents and of Velcade, respectively: thrombocytopenia (4 out of 8 patients), hypertension (3 out of 8 patients) and upper respiratory infection (3 out of 8 patients).

"We are very encouraged by the initial activity and the safety profile of MP0250 in combination with bortezomib and dexamethasone, even at the low dose of MP0250. We have started the treatment of the first two patients with the higher dose of 12 mg/kg which may be even more effective," said Andreas Harstrick, Chief Medical Officer of Molecular Partners.

Patrick Amstutz, CEO of Molecular Partners added: "These results further substantiate our development plans in multiple myeloma as well as the launch of our additional phase 1b/2 study of MP0250 in combination with osimertinib in EGFR-mutated NSCLC."

The ongoing Phase study of MP0250 in multiple myeloma is currently recruiting patients at the higher dose of 12mg/kg q3weeks. Overall, a total of at least 40 patients are planned to be treated. Additional safety and efficacy data are expected by the end of 2018.

An additional phase 1b/2 study will evaluate MP0250 in combination with osimertinib in patients with EGFR-mutated NSCLC pretreated with osimertinib (Tagrisso). The study is conducted in the US and is open for patient enrollment[2].

Full details on the Molecular Partners’ poster presentation today, from 5.30 to 7.00pm CET, at EHA (Free EHA Whitepaper) Stockholm can be found on the conference website. Following its presentation at EHA (Free EHA Whitepaper), the poster will also be available one the Molecular Partners website.

[1] ClinicalTrials.gov identifier NCT03136653

[2] ClinicalTrials.gov identifier NCT03418532

*DARPin is a registered trademark owned by Molecular Partners AG.

Financial Calendar
August 30, 2018 – Publication of 2018 Half-year Results
November 01, 2018 – Q3 2018 Management Statement
View Source

About MP0250
MP0250 is a multi-DARPin candidate targeting simultaneously VEGF and HGF, two prominent escape pathways, and has the potential to reverse resistance that has built to standard of care cancer therapies. Increases in VEGF and HGF are associated with disease progression in multiple myeloma and have been linked to poor prognosis. They are known to be able to stimulate neovascularization, bone destruction, and myeloma proliferation, migration, and adhesion in the bone marrow.

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.
With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in Phase 3, in partnership with Allergan.
Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in Phase 1 clinical development for the treatment of solid tumors and in Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has moved into Phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.

Karyopharm Presents Updated Selinexor Phase 1b/2 STOMP Myeloma Data from Multiple Combinations at the European Hematology Association 2018 Annual Meeting

On June 15, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that three posters highlighting clinical data from the ongoing Phase 1b/2 STOMP study in patients with multiple myeloma (MM) will be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2018 Annual Meeting taking place June 14-17, 2018 in Stockholm, Sweden (Press release, Karyopharm, JUN 15, 2018, View Source [SID1234527336]). These three poster presentations will feature updated data from the STOMP arms evaluating selinexor, the Company’s lead, novel, oral SINE compound, and dexamethasone in combination with standard approved therapies, Velcade (bortezomib), Pomalyst (pomalidomide) or Darzalex (daratumumab), in patients with previously treated MM.

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"The Phase 1b/2 STOMP study continues to generate important efficacy and safety data from the multiple ongoing arms evaluating selinexor and dexamethasone (dex) in combination with the standard approved therapies Velcade, Pomalyst and Darzalex in patients with multiple myeloma following at least one prior therapy," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "Based on the positive STOMP results reported to date, we have initiated a new all-oral STOMP arm to investigate selinexor plus Revlimid and dex in the front-line setting. Given the observed synergistic activity of selinexor with standard approved myeloma therapies, we believe oral selinexor has the potential to be a future backbone therapy in myeloma, and we look forward to elucidating its activity as part of a front-line treatment regimen."

Selinexor in Combination with Velcade and Low-dose Dexamethasone (SVd)

In the poster presentation titled, "Selinexor combined with low dose bortezomib and dexamethasone (SVd) induces a high response rate in patients with relapsed or refractory multiple myeloma (MM)," (Abstract code PS1322) Nizar Bahlis, MD, Southern Alberta Cancer Research Institute, will present updated clinical data from the SVd arm of the STOMP study. This study includes patients whose disease was proteasome inhibitor (PI) naïve, exposed or refractory, provided their disease was not refractory to Velcade as a last therapy. In this study arm, oral selinexor was dose-escalated in once-weekly (80 or 100mg) or twice-weekly (60 or 80mg) regimens. Velcade (1.3mg/m2 subcutaneously) was administered once-weekly or twice-weekly. Dex was administered orally either 40mg once-weekly or 20mg twice-weekly. The following table is a summary of the efficacy results:

Key: ORR=Overall Response Rate (sCR+CR+VGPR+PR), sCR=Stringent Complete Response, CR=Complete Response, VGPR=Very Good Partial Response, PR=Partial Response
1Responses were adjudicated according to the International Myeloma Working Group criteria
2Based on interim unaudited data
3Two patients not evaluable for response: one death unrelated to myeloma and one withdrawal of consent before disease follow up
4One unconfirmed PR
5Patient population eligible for the ongoing Phase 3, randomized BOSTON study evaluating SVd versus Vd. This a subset of the PI Relapsed/Naïve, ≤3 Prior Treatments

In the PI Relapsed/Naïve population (N=19), the ORR was 84% and the median PFS was 17.8 months with similar results in the "BOSTON" population (N=18). Nearly all patients (38 of 40) had reductions in M-protein, including 33% with a ≥90% reduction. This indication of efficacy in the SVd combination, with weekly Velcade and selinexor, warranted the further evaluation of SVd versus Vd in the BOSTON study given the previously reported ORR of 60-65% and PFS of 7-9 months in the Vd regimen among similar patient populations.

Among the 42 patients evaluable for safety, adverse events were consistent with those reported previously from the SVd arm of the STOMP study, with nausea (60%), anorexia (57%), fatigue (45%), diarrhea (40%), vomiting (29% and weight loss (24%) the most commonly reported Grade 1/2 events. Importantly, the reported peripheral neuropathy across all patients was Grade 1/2 and limited to six patients (14%), of which five had prior Velcade exposure. Grade 3/4 adverse events were also consistent with those reported previously with thrombocytopenia (45%), neutropenia (26%), fatigue (14%) and anemia (12%) being the most common. Based on the activity and tolerability observed in this study arm, the recommended Phase 2 dose (RP2D) regimen for SVd is oral selinexor (100mg once weekly), Velcade (1.3mg/m2 once-weekly subcutaneously) and oral dex (40mg weekly), which represents 40% less Velcade and 25% less dex compared to the approved standard Velcade + dex (Vd) regimen. This once weekly regimen is being evaluated in BOSTON.

Dr. Bahlis commented, "These updated data from the SVd arm of the STOMP study continue to show rapid time to response, high response rates, including an 83% ORR and the emergence of complete responses, along with a 17.8-month median PFS, in patients with relapsed or refractory myeloma. The combination also continues to be well tolerated with low rates of peripheral neuropathy. Importantly, these results are being achieved with 40% less Velcade and 25% less dex than the standard approved regimen, with no overt major organ toxicities."

Selinexor in Combination with Darzalex and Low-dose Dexamethasone (SDd)

In the poster presentation titled, "A Phase 1b study using the combination of selinexor, daratumumab, and dexamethasone in multiple myeloma patients previously exposed to proteasome inhibitors and immunomodulatory drugs," (Abstract code PS1329) Cristina Gasparetto, MD, Duke University Cancer Center, will present new clinical data from the SDd arm of the STOMP study evaluating myeloma patients who received at least three prior lines of therapy, including a PI and an immunomodulatory drug (IMiD), or patients with myeloma refractory to both a PI and an IMiD. In this study arm, oral selinexor was dose escalated using either 100mg once weekly or 60mg twice weekly, with Darzalex (16mg/kg intravenously once weekly) and dex (orally, 40mg once weekly or 20mg twice weekly).

Key: ORR=Overall Response Rate (VGPR+PR)
1Responses were adjudicated according to the International Myeloma Working Group criteria
2Based on interim unaudited data
3One patient not evaluable for response withdrew consent prior to disease follow up, one patient pending response
4 Three unconfirmed PR

Despite the heavily pretreated nature of the patients in the study, with 100% of the patients having dual- (PI and IMID-) refractory disease, responses occurred rapidly, with a median of one month to onset; 12 of the 19 patients remain on treatment. Based on published data the expected ORR for Darzalex therapy without selinexor in the Darzalex-naïve population is ~30%. Thus, the ORR of 82% provides a basis for further evaluation of the weekly SDd combination.

Among the 21 patients evaluable for safety, the most common Grade 1/2 adverse events were nausea (48%), fatigue (38%), diarrhea (24%), constipation (24%), and anorexia (24%). The most common Grade 3/4 adverse events were thrombocytopenia (48%), leukopenia (43%), anemia (33%), neutropenia (33%) and decreased lymphocyte count (24%). Gastrointestinal adverse events were generally manageable with supportive care. The maximum tolerated dose was not reached. Two DLTs (Grade 3 thrombocytopenia and Grade 2 fatigue) were observed in patients receiving selinexor 60mg twice weekly; both patients showed responses. Based on the preliminary tolerability and efficacy data, the RP2D of SDd is selinexor (100mg orally, once weekly), Darzalex (16mg/kg, once weekly) and dex (40mg orally, weekly).

Dr. Gasparetto commented, "These preliminary results from the SDd arm of the STOMP study show high response rates, including an 82% ORR in Darzalex-naïve patients with refractory myeloma. This combination regimen appears to be well tolerated with responses observed rapidly occurring within a median one cycle of treatment. We look forward to continuing enrollment in this treatment arm."

Selinexor in Combination with Pomalyst and Low-dose Dexamethasone (SPd)

In the poster presentation titled, "Selinexor combined with pomalidomide and low dose dexamethasone (SPd) in a relapsed/refractory multiple myeloma patient population," (Abstract code PF586) Christine Chen, MD, FRCP, University of Toronto, Princess Margaret Cancer Center, will present updated clinical data from the SPd arm of the STOMP study which includes patients with multiple myeloma who previously received Revlimid and a PI. In this study arm, selinexor was dosed orally either once weekly (80 or 100mg) or twice weekly (60 or 80mg) with Pomalyst (3 or 4mg orally, once daily) and dexamethasone (dex; orally, 40mg once weekly or 20mg twice weekly). The following table is a summary of the efficacy results:

Key: ORR=Overall Response Rate (VGPR+PR)
1Responses were adjudicated according to the International Myeloma Working Group criteria
2Based on interim unaudited data
3Four patients not evaluable for response: one death unrelated to myeloma, one non-compliance with study procedures, two withdrawal of consent before disease follow up
4One unconfirmed PR

Responses tended to occur rapidly with a median of one month to onset. Median PFS among all evaluable patients was 10.3 months, with a follow up of 9.4 months. The efficacy of the SPd combination warrants further clinical evaluation.

Among the 34 patients evaluable for safety, the most common Grade 1/2 adverse events were anorexia (56%), nausea (47%), fatigue (41%), weight loss (38%), diarrhea (26%) and thrombocytopenia (26%). The most common Grade ≥3 adverse events were neutropenia (56%), thrombocytopenia (32%) and anemia (29%). Gastrointestinal adverse events were generally manageable with supportive care. There were two Grade 5 treatment-related events (febrile neutropenia and intracranial hemorrhage). Six DLTs (Grade 3 fatigue, febrile neutropenia, hyponatremia, neutropenia and thrombocytopenia) were observed in patients receiving selinexor 60mg twice weekly, 80mg twice weekly and 80mg once weekly. Based on the activity and tolerability observed in this study arm, doses of oral selinexor 60-80mg once weekly are being evaluated in combination with Pomalyst (3mg orally, once daily) and low dose dex to determine the RP2D for this combination regimen.

Dr. Chen stated, "This novel, all oral regimen continues to demonstrate strong response rates, including a 55% ORR, along with an 11.6-month median PFS, in Pomalyst-naïve and Revlimid-relapsed or -refractory patients. In this STOMP arm, once-weekly selinexor has been generally well tolerated and rapidly induced durable responses in patients with PI- and Revlimid-exposed myeloma."

Details for the EHA (Free EHA Whitepaper) 2018 presentations are as follows:

Company-sponsored Trials

Title: Selinexor combined with low dose bortezomib and dexamethasone (SVd) induces a high response rate in patients with relapsed or refractory multiple myeloma (MM)
Lead author: Nizar Bahlis, Southern Alberta Cancer Research Institute
Final Abstract Code: PS1322
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time: Saturday, June 16, 2018; 17:30 – 19:00 CEST
Location: Poster area

Title: A Phase 1b study using the combination of selinexor, daratumumab, and dexamethasone in multiple myeloma patients previously exposed to proteasome inhibitors and immunomodulatory drugs
Lead author:Cristina Gasparetto, Duke University
Final Abstract Code: PS1329
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time: Saturday, June 16, 2018; 17:30 – 19:00 CEST
Location: Poster area

Title: Selinexor combined with pomalidomide and low dose dexamethasone (SPd) in a relapsed/refractory multiple myeloma patient population
Presenter:Christine Chen, University of Toronto, Princess Margaret Cancer Center
Final Abstract Code: PF586
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:Friday, June 15, 2018; 17:30 – 19:00 CEST
Location: Poster area

Investigator-sponsored Trials

Title: A Phase II study of selinexor (KPT-330) combined with bortezomib and dexamethasone (SVD) for induction and consolidation for patients with progressive or refractory multiple myeloma; the selvedex trial
Lead author: Annemiek Broijl, Erasmus MC Cancer Institute
Final Abstract Code: PS1338
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time: Saturday, June 16, 2018; 17:30 – 19:00 CEST
Location: Poster area

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,400 patients have been treated with selinexor. In April 2018, Karyopharm reported positive top-line data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation by the U.S Food and Drug Administration (FDA) for the patient population evaluated in the STORM study. Karyopharm plans to submit a New Drug Application (NDA) to the FDA during the second half of 2018, with a request for accelerated approval for oral selinexor as a new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON) and as a potential backbone therapy in combination with approved therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

New long-term data confirm Roche’s Gazyva/Gazyvaro extends the lives of people with chronic lymphocytic leukaemia compared to MabThera/Rituxan

On June 15, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported data from the final analysis of the CLL11 study evaluating Gazyva/Gazyvaro (obinutuzumab)-based treatment in previously untreated chronic lymphocytic leukaemia (CLL) which will be presented during the Presidential Symposium at the 23rd European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress, 14 – 17 June, in Stockholm (Press release, Hoffmann-La Roche, JUN 15, 2018, View Source [SID1234527335]). After a follow-up of nearly five years, final results showed clinically meaningful improvements with Gazyva/Gazyvaro plus chlorambucil across multiple endpoints, including progression-free survival (PFS) and overall survival (OS), when compared head-to-head with MabThera/Rituxan (rituximab) plus chlorambucil. Gazyva/Gazyvaro-based treatment reduced the risk of death by 24% compared to MabThera/Rituxan-based treatment (median OS not reached vs. 73.1 months, HR= 0.76; 95% CI 0.60-0.97; p<0.0245). These new data add to the growing body of evidence for the OS benefit with Gazyva/Gazyvaro in first-line CLL after the previously reported OS benefit with Gazyva/Gazyvaro combined with chlorambucil versus chlorambucil alone.

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"We are very pleased that the majority of patients treated with Gazyva/Gazyvaro are still alive after nearly five years of follow-up in the CLL11 study," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "This meaningful survival benefit compared to MabThera/Rituxan-based therapy reinforces that Gazyva/Gazyvaro-based therapy is an important option for people with previously untreated CLL."

After a median observation time of nearly five years (59.4 months) this final analysis of the CLL11 study demonstrated:

A reduction in the risk of disease progression or death of 51% for patients treated with Gazyva/Gazyvaro plus chlorambucil versus those treated with MabThera/Rituxan plus chlorambucil (median PFS 28.9 vs. 15.7 months, HR= 0.49; 95% CI 0.41-0.58; p<0.0001).
A clinically meaningful improvement in OS for patients receiving Gazyva/Gazyvaro plus chlorambucil compared to MabThera/Rituxan plus chlorambucil. At the time of final analysis the median OS in the Gazyva/Gazyvaro plus chlorambucil arm was not yet reached which means that more than half of these patients were still alive after nearly five years. A 24% reduction in the risk of death was observed with Gazyva/Gazyvaro plus chlorambucil treatment (median OS not reached vs. 73.1 months, HR= 0.76; 95% CI 0.60-0.97; p<0.0245).
A prolonged time to initiation of the next therapy (time to new treatment; TTNT) with Gazyva/Gazyvaro plus chlorambucil (median 56.4 vs. 34.9 months, Gazyva/Gazyvaro plus chlorambucil vs. MabThera/Rituxan plus chlorambucil, HR= 0.58; 95% CI 0.46-0.73; p<0.0001).
Patients treated with Gazyva/Gazyvaro plus chlorambucil achieved a higher rate of minimal residual disease (MRD) negativity versus those treated with MabThera/Rituxan plus chlorambucil (24% vs. 2% of patients MRD-negative, Gazyva/Gazyvaro plus chlorambucil vs. MabThera/Rituxan plus chlorambucil). Being MRD negative means no cancer can be detected in the blood and or bone marrow using a sensitive test.
No new or unexpected safety concerns for the combination of Gazyva/Gazyvaro plus chlorambucil.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil, for people with previously untreated CLL, based on previously reported data from the CLL11 study.1

About the CLL11 study
CLL11 is a phase III, multicenter, open-label, randomised three-arm study to investigate the safety and efficacy profile of Gazyva/Gazyvaro plus chlorambucil compared to MabThera/Rituxan plus chlorambucil or chlorambucil alone in nearly 800 people with previously untreated CLL and comorbidities. The primary endpoint of the study is PFS with secondary endpoints including response rate, molecular remission rate, OS, TTNT and safety profile. In terms of analysis, the study was divided into three stages:

Stage 1a compared the addition of Gazyva/Gazyvaro to chlorambucil vs. chlorambucil alone
Stage 1b compared the addition of MabThera/Rituxan to chlorambucil vs. chlorambucil alone
Stage 2 compared Gazyva/Gazyvaro plus chlorambucil to MabThera/Rituxan plus chlorambucil
About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia (CLL), in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 60 countries in combination with chemotherapy for previously untreated, follicular lymphoma.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world. 2 CLL mainly affects men and the median age at diagnosis is about 70 years.3 Worldwide, the incidence of all leukaemias is estimated to be over 350,000 and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.4

About Roche in haematology