On December 11, 2017 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported updated data from its completed pilot study1 of NY‑ESO SPEAR T-cell therapy in multiple myeloma patients in the setting of autologous stem cell transplant (ASCT) presented by the main investigator at the annual ASH (Free ASH Whitepaper) meeting (Press release, Adaptimmune, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322198 [SID1234522540]).

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"Mature data from this study in multiple myeloma continues to show promising efficacy and acceptable safety," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "We have observed a high response rate, long response duration, and encouraging long‑term survival in this population of patients with poor prognosis, treatment refractory myeloma. In addition, NY-ESO SPEAR memory T-cells persist long-term and respond to antigen after more than three years post‑treatment. NY-ESO SPEAR T-cell therapy is currently being evaluated in a second study in multiple myeloma patients with or without KEYTRUDA, all without stem cell transplant."

Long-term follow up data from the pilot study of NY-ESO in multiple myeloma in the context of ASCT

During an oral presentation, Dr. Edward Stadtmauer, University of Pennsylvania Abramson Cancer Center, presented an update on all twenty-five multiple myeloma patients treated in Adaptimmune’s pilot study in the setting of ASCT. The data cut-off for this oral presentation was August 16, 2017.

Overall Conclusions

NY-ESO SPEAR T-cell therapy in the setting of ASCT has promising efficacy and acceptable safety in multiple myeloma patients
Durable responses and long-term survival demonstrated in this refractory population
NY-ESO SPEAR T-cells persisted long term (>1000 days), but were are not exhausted
The most common adverse events (summarized below) were generally not unexpected in this patient population
Persisting cells produced multiple cytokines in response to antigen
Persisting cells included highly differentiated effector subsets and a population of self-renewing stem cell memory cells
A follow up study is ongoing in combination with KEYTRUDA, which will transition to GSK
Efficacy Results

Of the twenty-five patients treated in this study, 11 were alive at data cut-off
Three patients remain disease-progression free at 3, 4.5, and 5 years post-treatment
Five of 18 subjects tested were minimal residual disease negative at day 100
The median duration of response was >12 months
The median predicted overall survival is approximately three years
Overall response rate (ORR) at 100 days and one year were 76% and 44%, respectively, using International Myeloma Working Group criteria
Safety Results

There were no fatal adverse events (AEs), and cytokine release syndrome was not reported
Autologous graft versus host disease (GvHD) was reported in six patients; all resolved with corticosteroids and supportive therapy
Most common AEs (any grade AE occurring in >50% of patients) included diarrhea (100%), nausea (100%), anemia (96%), thrombocytopenia (92%), fatigue (88%), pyrexia (84%), rash (84%), hypokalemia (76%), febrile neutropenia (72%), vomiting (72%), neutropenia (68%), back pain (60%), leukopenia (60%), cough (56%), dyspnea (56%), hypocalcemia (56%), peripheral edema (56%), stomatitis (56%), and abdominal pain (52%).
Exploratory Endpoints

TCR-transduced NY-ESO SPEAR T-cells persisted long term (>1000 days) with minimal expression of exhaustion markers, and persisting cells:
Were functional, producing multiple cytokines in response to antigen in vitro
Included highly differentiated effector subsets and a population of self-renewing stem cell memory cells

On December 11, 2017 Seattle Genetics, Inc. (NASDAQ:SGEN) and Bristol-Myers Squibb Company (NYSE:BMY) reported highlighted updated interim results from an ongoing phase 1/2 clinical trial evaluating the combination of ADCETRIS (brentuximab vedotin) and Opdivo (nivolumab) in relapsed or refractory classical Hodgkin lymphoma (HL) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Atlanta, Georgia, December 9-12, 2017 (Press release, Seattle Genetics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322109 [SID1234522562]). The data were also simultaneously published online in the journal Blood. The data reported from 62 patients, including 60 evaluable for response, were featured in an oral presentation and selected to be included in the 2018 Highlights of ASH (Free ASH Whitepaper) post-meeting program. 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 HL or for other indications.

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"The phase 1/2 study combining the antibody-drug conjugate ADCETRIS with the PD-1 immune checkpoint inhibitor Opdivo is a promising investigational approach as it combines a CD30-targeted therapy with a therapy designed to activate the immune system. The antitumor activity of the drugs may be enhanced when administered in combination," said Alex Herrera, M.D., lead trial investigator and assistant professor at the City of Hope Medical Center, Duarte, California. "The interim results evaluating the combination regimen in relapsed or refractory HL patients continue to look compelling, demonstrating both promising activity in addition to a manageable overall safety profile. These data support further exploration of this novel, chemotherapy-free investigational regimen in HL patients."

"We are evaluating ADCETRIS broadly as the foundation of care for CD30-expressing lymphomas, including combination strategies that have the potential to improve efficacy. At this year’s ASH (Free ASH Whitepaper) Annual Meeting, we are presenting significant clinical updates that support this goal, including results from the phase 3 ECHELON-1 clinical trial evaluating ADCETRIS in combination with chemotherapy in frontline HL as well as interim results from this phase 1/2 study evaluating ADCETRIS in combination with Opdivo in relapsed HL," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "Interim results from the trial evaluating ADCETRIS in combination with Opdivo as pre-transplant salvage therapy for classical HL patients continue to look promising, demonstrating an 83 percent objective response rate, with a 62 percent complete response rate and an acceptable safety profile. We look forward to further evaluation of this innovative combination regimen in other disease settings, including the ongoing pivotal phase 3 CHECKMATE 812 study in patients with relapsed HL, in partnership with Bristol-Myers Squibb."

"Our ongoing collaboration to evaluate Opdivo in combination with Seattle Genetics’ ADCETRIS reinforces Bristol-Myers Squibb’s commitment to addressing cancer from all angles for patients with high unmet needs," said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. "We look forward to further evaluation of the ADCETRIS and Opdivo combination in Hodgkin lymphoma and other hematologic malignancies in several ongoing trials."

Interim Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma (Abstract #649, oral presentation at 10:30 a.m. ET)

Data were reported from 62 patients with relapsed or refractory HL who received the combination regimen of ADCETRIS plus Opdivo after failure of frontline therapy. 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 autologous stem cell transplant (ASCT). The median age of patients was 36 years. The majority of patients (95 percent) were refractory or had relapsed after receiving the standard of care frontline treatment ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or some variation of the standard of care (ABVE-PC, R-ABVD).

Key findings presented include:

Of 60 response-evaluable patients, 50 patients (83 percent) had an objective response, including 37 patients (62 percent) with a complete response and 13 patients (22 percent) with a partial response. Five patients (eight percent) had stable disease and five patients (eight percent) had progressive disease. Median follow-up time was eight months and median duration of response was not yet reached. The estimated six-month progression-free survival rate was 89 percent.
Of the 62 patients enrolled, 58 patients completed all four cycles of study treatment and four patients discontinued prior to the end of treatment. At the time of data analysis, 54 patients received an ASCT. Preliminary analysis shows no impact of combination treatment with ADCETRIS and Opdivo on stem cell mobilization or engraftment.
The most common adverse events (AEs) of any grade occurring prior to ASCT or subsequent salvage therapy in at least 20 percent of patients were nausea, fatigue, infusion-related reaction (IRR), pruritus, diarrhea, headache, cough, vomiting, dyspnea, nasal congestion, pyrexia and rash. Grade 3 or 4 adverse events occurred in 19 patients (31 percent), with 17 patients (28 percent) having Grade 3 AEs (fatigue, IRR, pruritus and diarrhea) and two patients (three percent) having Grade 4 AEs (thrombocytopenia and increased lipase).
Infusion-related reactions (IRRs) were observed in 44 percent of patients, of which the majority (41 percent) were Grade 1 or 2. No patients discontinued treatment due to an IRR.
Potential immune-related adverse events, excluding IRRs, occurred in 50 patients (82 percent), and five patients required treatment with systemic steroids, including patients with Grade 3 diarrhea and Grade 2 colitis, Grade 3 aspartate aminotransferase elevation, Grade 4 colitis and pneumonitis (after receiving additional salvage therapy), Grade 2 pneumonitis, and Grade 4 pneumonitis (after BEAM, as part of the conditioning regimen). No patients discontinued treatment due to an immune-related adverse event.
ADCETRIS and Opdivo are being evaluated as combination therapy in multiple ongoing clinical trials. In addition to the study presented at ASH (Free ASH Whitepaper), a trial titled "A Safety and Effectiveness Study of Nivolumab in Combination With Brentuximab Vedotin to Treat Non-Hodgkin Lymphomas" is ongoing and enrolling patients with relapsed or refractory disease, including diffuse large B-cell lymphoma (DLBCL), and other rare subtypes of B-cell lymphoma, including mediastinal B-cell lymphoma and mediastinal gray zone lymphoma. The companies have also extended the clinical evaluation of ADCETRIS and Opdivo into a clinical trial evaluating the combination as frontline treatment for older HL patients. Lastly, the companies initiated a pivotal phase 3 clinical trial called CHECKMATE 812 trial evaluating ADCETRIS alone versus ADCETRIS in combination with Opdivo in relapsed/refractory 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% 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, approximately 8,260 cases of Hodgkin lymphoma will be diagnosed in the United States during 2017 and more than 1,000 will die from the disease. According to the Lymphoma Coalition, over 62,000 people worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30 and is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

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 four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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

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

ADCETRIS has received marketing authorization by regulatory authorities in 69 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

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

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 + Yervoy combination 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.

On December 11, 2017 Atara Biotherapeutics, Inc. (Nasdaq:ATRA), a leading off-the-shelf T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that the Company’s collaborating investigators presented updated, positive interim results for tabelecleucel (formerly known as ATA129) from a multicenter expanded access protocol (EAP) study for patients with EBV associated cancers (Press release, Atara B59thiotherapeutics, DEC 11, 2017, View Source [SID1234522568]). The findings were reported at the ongoing 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in Atlanta, GA, December 9-12, 2017. Tabelecleucel is Atara’s off-the-shelf T-cell immunotherapy in development for the treatment of Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+PTLD), as well as other EBV associated hematologic and solid tumors.

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"We are gratified to see that the multicenter clinical findings in patients with EBV+PTLD are consistent with the tabelecleucel profile observed in the Phase 2 studies conducted at Memorial Sloan Kettering Cancer Center," said Chris Haqq M.D., Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer of Atara Biotherapeutics. "We look forward to initiating Phase 3 clinical studies with tabelecleucel by the end of this year, which are expected to enroll the same EBV+PTLD patient populations as presented at ASH (Free ASH Whitepaper)."

Updated efficacy findings were presented:

In 6 patients with rituximab-refractory EBV+PTLD following solid organ transplant (SOT) the Objective Response Rate (ORR) was 83%, with 5 of 6 patients responding to treatment.
Additionally, in 5 patients with rituximab-refractory EBV+PTLD following allogeneic hematopoietic cell transplant (HCT) an ORR of 80% was observed, with 4 of 5 patients responding to treatment.
An additional patient with EBV+PTLD following HCT remains alive, but was not evaluable due to lack of post-baseline assessment.
The estimated one-year overall survival for the 12 tabelecleucel treated patients with EBV+PTLD following HCT or SOT, was 90.9% [95% confidence interval (50.8%, 98.7%)].
Updated safety findings were reported for a total of 23 patients, including an additional 11 patients with other EBV associated cancers who were included in the safety analysis:

Tabelecleucel was generally well-tolerated in this study population, which comprised quite ill, mostly immunosuppressed patients with multiple comorbidities.
5 patients experienced treatment-related serious adverse events (SAEs).
One HCT patient died due to PTLD disease progression.
Two possibly related cases of graft-versus-host disease (GvHD) in patients with EBV+PTLD following HCT were reported.
A tumor flare was observed in one patient with EBV+ HIV-associated plasmablastic lymphoma that resolved without clinical sequelae.
Atara’s collaborating investigators at Memorial Sloan Kettering Cancer Center presented updated results for ATA230, an allogeneic T-cell immunotherapy targeting antigens expressed by cytomegalovirus (CMV), from 50 post-transplant patients with refractory CMV viremia and disease, including those with disease in the CNS. The reported response rate of 64% in all patients was similar in those with CMV viremia and disease. Patients who responded to ATA230 showed improved 6-month survival of 81.3% versus 33.3% in patients who did not respond to treatment. One of the 32 patients who responded to ATA230 died of CMV disease. ATA230 was generally well-tolerated. Five patients experienced grade 4 or 5 serious adverse events deemed possibly related to ATA230.

About EBV+PTLD
Since its discovery as the first human oncovirus, Epstein-Barr virus (EBV) has been implicated in the development of a wide range of lymphoproliferative disorders, including lymphomas and other cancers. EBV is widespread in all human populations and persists as a lifelong, asymptomatic infection. In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), EBV associated post-transplant lymphoproliferative disorder (EBV+PTLD), represents a life-threatening condition. Median overall survival in patients with EBV+PTLD following HCT who have failed rituximab-based first line therapy is 16-56 days. In EBV+PTLD following SOT, patients failing rituximab experience increased chemotherapy-induced treatment-related mortality compared to other lymphoma patients. One- and two-year survival in patients with high-risk EBV+PTLD following SOT is 36% and 0%, respectively.

About tabelecleucel (formerly known as ATA129)
Atara’s most advanced T-cell immunotherapy in development, tabelecleucel, is a potential treatment for patients with rituximab-refractory Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (EBV+PTLD), as well as other EBV associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC). In February 2015, FDA granted tabelecleucel Breakthrough Therapy Designation for EBV+PTLD following allogeneic hematopoietic cell transplant (HCT) and in October 2016, tabelecleucel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. Atara also received positive regulatory feedback from Health Canada in September 2017 supporting the submission of tabelecleucel for an expedited approval pathway. In addition, tabelecleucel has orphan status in the U.S. and EU. Phase 3 studies of tabelecleucel in EBV+PTLD following HCT (MATCH study) or solid organ transplant (ALLELE study) are expected to start in 2017, and a Phase 1/2 study in NPC is planned for 2018. Tabelecleucel is also available to eligible patients with EBV associated hematologic and solid tumors through an ongoing multicenter expanded access protocol (EAP) clinical study.

About CMV
In patients with weakened immune systems, including bone marrow and solid organ transplant recipients, newborns with immature immune systems and those with human immunodeficiency virus (HIV), cytomegalovirus (CMV) can cause potentially life-threatening disease or may result in blindness, brain damage, and deafness. While small molecule antiviral drugs are approved to treat and prevent CMV infection, there remains a high unmet need due to viral resistance, modest neurodevelopmental activity and adverse effects, such as toxicity and reduction in white blood cell count impairing the ability to fight other infections, with these agents.

About ATA230
ATA230, an allogeneic T-cell immunotherapy targeting antigens expressed by cytomegalovirus (CMV), has been investigated in one Phase 1 and two Phase 2 clinical studies in immunocompromised patients with CMV viremia or disease who are refractory or resistant to antiviral drug treatment in the post-transplant setting. In October 2017, Atara announced that ATA230 was granted Rare Pediatric Disease Designation by the FDA for the treatment of congenital CMV infection, and in September 2017, ATA230 received orphan drug designation in the U.S. for the treatment of CMV viremia and disease in immunocompromised patients. The European Medicines Agency (EMA) in October 2016 also issued a positive orphan drug designation opinion for ATA230 for the treatment of CMV infection in patients with impaired cell-mediated immunity. Atara intends to further evaluate ATA230 development plans with the FDA and other global health authorities following the initiation of tabelecleucel EBV+PTLD Phase 3 studies.

On December 11, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMmotion151 study met its co-primary endpoint of investigator-assessed progression-free survival (PFS) and demonstrated that the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) provided a statistically significant and clinically meaningful reduction in the risk of disease worsening or death (PFS) in people whose disease expressed the PD-L1 (programmed death-ligand 1: Expression ≥1%) protein compared with sunitinib for the first-line treatment of people who have advanced or metastatic renal cell carcinoma (mRCC) (Press release, Hoffmann-La Roche, DEC 11, 2017, View Source [SID1234522504]).

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Observations of a pre-specified subgroup analysis of the Tecentriq and Avastin combination indicated that, in people whose disease expressed PD-L1, a numerical difference favouring Tecentriq was seen across all patient risk factor groups (favourable, intermed­iate and poor) compared to sunitinib; however, due to the study design these data could not be assessed for statistical significance and are descriptive only. Assessment of secondary endpoints is ongoing. Safety for the Tecentriq and Avastin combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the Phase II IMmotion150 study. No new safety signals were identified with the combination.

Results will be presented at an upcoming oncology conference in 2018. Top-line results from the co-primary endpoint of overall survival (OS) are not mature.

"We are encouraged by these results as they add to the emerging body of evidence that supports our rationale for this combination. We believe that the regimen of Tecentriq and Avastin may enhance the potential of the immune system in the initial treatment of advanced kidney cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We will discuss these data with health authorities globally and hope to bring this combination forward as a potential new treatment option to patients as soon as possible.’’
IMmotion151 is the second successive positive Phase III study of Tecentriq that includes an Avastin combination component as an initial treatment. This follows the positive Phase III non-squamous non-small cell lung cancer (NSCLC) IMpower150 study that showed Tecentriq and Avastin plus chemotherapy demonstrated a PFS advantage over Avastin plus chemotherapy.

About the IMmotion151 study
IMmotion151 is a Phase III multicentre, randomised, open-label study to evaluate the efficacy and safety of Tecentriq and Avastin versus sunitinib in people with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. It enrolled 915 people globally who were randomised 1:1 to receive Tecentriq and Avastin, or sunitinib alone.

People in the Tecentriq and Avastin arm received Tecentriq at a fixed dose of 1200 milligrams (mg) and Avastin at a dose of 15 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 3 weeks until loss of clinical benefit or unacceptable toxicity. People in the sunitinib arm received sunitinib 50 mg orally, once daily for 4 weeks followed by 2 weeks rest until loss of clinical benefit or unacceptable toxicity.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in people whose tumours expressed PD-L1 [PD-L1 expression ≥1 percent on immune cells (IC)], and OS in the overall study population (intention-to-treat, ITT). PD-L1 expression was prospectively assessed using an immunohistochemistry (IHC) test (SP142) developed by Roche Tissue Diagnostics.
Stratification factors included the presence or absence of liver metastases; level of IC staining for PD-L1 (≥1 percent vs. <1 percent) and Memorial Sloan-Kettering Cancer Center (Motzer) risk score. The Motzer prognostic scoring system predicts for OS based upon an individual’s baseline clinical and laboratory characteristics.
Depending on the presence of one or several of five variables (risk factors), patients are classified in one of the three risk groups: ‘Favourable’ with 0 risk factors, ‘Intermediate’ with 1–2 risk factors and ‘Poor’ with ≥ 3 risk factors.

About RCC
Kidney cancer remains one of the most common cancers in the world, accounting for over 140,000 deaths worldwide each year,1 with renal cell carcinoma (RCC) accounting for approximately 90% of all cases.2 Over 300,000 people are diagnosed with RCC every year and currently only about 1 in 10 people are alive beyond 5 years following diagnosis of metastatic disease.

RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where our blood is filtered.4 Typically, RCC is a single tumour in one kidney but, in rare cases, there can be multiple tumours, which can occur in one or both kidneys.

Despite recent progress in the field of kidney cancer, treatment options for people with the disease remains limited.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Tecentriq is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Avastin (bevacizumab) in RCC
Avastin (bevacizumab) is an anti-VEGF inhibitor. VEGF (vascular endothelial growth factor) is a protein that stimulates the formation and maintenance of blood vessels and has been shown to play a key role in the development of RCC.
RCC tumours are highly vascularised, meaning they have many blood vessels and also exhibit a high concentration of VEGF5. There is, therefore a strong rationale for medicines such as Avastin that block the VEGF pathway. Avastin is the only currently available treatment for patients with mRCC that directly inhibits VEGF.

There is a strong scientific rationale to support further investigation of Tecentriq and Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat first-line advanced NSCLC and mRCC. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.
To learn more about the Roche approach to cancer immunotherapy please follow this link:
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On December 11, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment; TecDAX, OTC: MPSYY) reported clinical data from the ongoing phase 2 clinical trial (L-MIND) evaluating MOR208 in combination with lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). DLBCL is the most frequent type of malignant lymphoma worldwide and accounts for approximately 30% of all non-Hodgkin lymphomas. Data will be reported in a poster presentation (available for download) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia/USA. MOR208 is an investigational Fc-engineered monoclonal antibody directed against CD19 (Press release, MorphoSys, DEC 11, 2017, View Source [SID1234522518]).

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The data presented at ASH (Free ASH Whitepaper) formed the basis for the Breakthrough Therapy designation recently awarded by the FDA for MOR208, in combination with lenalidomide, for the treatment of non-transplant eligible patients with R/R DLBCL.

At data cut-off (June 13, 2017), 51 patients had been enrolled in the study, of whom 44 were evaluable for efficacy assessments. Preliminary data show an objective response in 23 out of 44 patients (ORR: 52%), 19 (83%) of whom show ongoing responses. Complete remission was seen in 14 out of 44 patients (CR: 32%). The median time to response was 1.8 months, the median time to complete response was 2.3 months. The preliminary median progression-free survival (PFS) based on Kaplan Meier calculation was 11.3 months.

No unexpected toxicities were observed for the treatment combination and no infusion-related reactions were reported for MOR208. The most frequent adverse events with a toxicity grading of 3 or higher were neutropenia, thrombocytopenia, and leukopenia, observed in 35%, 10%, and 8% of patients, respectively. Pneumonia and hypokalemia were reported for 10% and 8% of the patients. To date, 45% of patients required a reduction of their lenalidomide dose, from a starting dose of 25mg daily.

The trial has recently completed patient recruitment as required by the study protocol. To date, 81 patients have been enrolled.

"We are very encouraged by the updated clinical trial results from the ongoing L-MIND trial, especially the complete responses and the duration of responses we have seen so far. DLBCL is a very aggressive lymphoma. In particular, those patients with relapsed or refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplantation are in need of more therapeutic options. Based on the FDA Breakthrough Therapy designation we recently obtained, we intend to develop MOR208 together with lenalidomide as a potential new treatment option for this patient group as quickly as possible," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG.

The L-MIND trial (Lenalidomide plus MOR208 in DLBCL) is a single-arm, open-label, multicenter study of MOR208 in combination with lenalidomide. The trial is enrolling patients with relapsed or refractory DLBCL after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy (e.g. rituximab). Patients could not be candidates for high-dose chemotherapy and autologous stem cell transplantation. Patients enrolled had a median age of 74 years.

Details of the MOR208 presentation at ASH (Free ASH Whitepaper) 2017:

Abstract #4123; Poster III

Single-Arm Phase II Study of MOR208 Combined with Lenalidomide in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: L-Mind

The poster will be presented during the session #626 "Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials" on Monday, December 11, 2017, 6:00pm-8:00pm EST (Dec. 12, 2017, 0:00am-2:00am CET), in the Georgia World Congress Center, Bldg A, Lvl 1, Hall A2.

In addition to the presentation, the abstract has been published online in the December 8, 2017 supplemental volume of Blood. Additional information can be found at www.hematology.org, including the abstract.

MorphoSys will hold an investor & analyst conference call after the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2017 on December 12, 2017, 11:00am EST(5:00pm CET).

Dial in:
Germany: +49 89 2444 32975
United Kingdom: +44 20 3003 2666
USA: +1 202 204 1514
The presentation slides and webcast link will be available at www.morphosys.com/conference-calls. A slide-synchronized audio replay of the conference will also be available at the corporate website following the live event.

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 Fc-enhanced monoclonal antibody directed against CD19, a prominent marker present on the surface of B-cells. 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. Furthermore, 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 AG 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) was started in March 2016 and is designed to investigate the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL. The phase 2/3 B-MIND study was started in August 2016 and transitioned into its phase 3 pivotal part in June 2017 following a recommendation of the IDMC based on the available data from the phase 2 initial safety evaluation. The B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Furthermore, MOR208 is currently being clinically investigated in combination with idelalisib or venetoclax in patients with relapsed/refractory CLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib).