On June 11, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that data from the pilot study of NY-ESO SPEAR T‑cells in synovial sarcoma will be published in Cancer Discovery (an American Association of Cancer Research [AACR] publication) (Press release, Adaptimmune, JUN 11, 2018, View Source;p=RssLanding&cat=news&id=2353966 [SID1234527255]). Beyond the clinical data, some of which having been reported previously (most recently at CTOS 2017 [https://bit.ly/2mtk13W]), this peer-reviewed paper provides new insights into SPEAR T-cells and the responses they mediate in patients.

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GlaxoSmithKline plc (LSE:GSK) (NYSE:GSK) exercised its option to exclusively license the right to research, develop, and commercialize NY‑ESO SPEAR T-cell therapy program in September 2017. Transition of this program to GSK is ongoing.

"Metastatic synovial sarcoma is virtually incurable with standard therapy. NY-ESO SPEAR T‑cells can mediate durable antitumor responses in these patients," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "Data published in Cancer Discovery highlight that our persisting SPEAR T-cells comprise a robust, self-regenerating pool of polyfunctional, non-exhausted T-cells capable of antitumor effects despite prolonged exposure to antigen. Our efforts to better understand the characteristics of our SPEAR T-cells post-infusion will continue as we strive to bring the most effective therapies to patients."

"The results of the study are encouraging," said Dr Sandra D’Angelo, medical oncologist at Memorial Sloan Kettering Cancer Center. "Through this research and these results we are understanding how to better treat synovial sarcoma."

Data from Cohort 1 of the synovial sarcoma pilot study, based on twelve patients treated, included in the peer reviewed paper (data cut off 30 March 2017), is summarized below.

Compelling response data

Median duration of response of 30.9 weeks (range 13-72 weeks)
Overall response rate of 50% (6/12 patients), and 60% among the ten patients who received the target dose of at least one billion transduced cells
There was one confirmed complete response and five confirmed partial responses
Median time to initial response of 6.2 weeks (range 4-9 weeks)
Encouraging survival data

Median progression-free survival (PFS) was 15 weeks (range 8-38 weeks)
The current estimate of the median overall survival is approximately 120 weeks among the twelve patients in Cohort 1 (range 37 weeks-undetermined value, as the upper bound has not been reached)
Characteristics of antitumor responses indicate effects are immune-mediated

Maximal effects of chemotherapy are typically observed within four weeks of treatment; however, seven patients experienced continued decreases in tumor burden following the four week evaluation point, and maximal antitumor responses occurred in four patients more than three months post-infusion
There was also demonstration of transient increases in the size of metastatic lesions consistent with lymphocyte-induced inflammation followed by regression as well as trafficking of SPEAR T‑cells into the tumor bed, indicating that, unlike currently available immune therapies, these cells can kill cancer cells in previously non-inflamed tumors
Acceptable safety profile

The majority of adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies.
There were no fatal serious adverse events in this treatment cohort
The most common adverse events ≥ grade 3 were lymphopenia (100%), leukopenia (92%), neutropenia (83%), anemia (83%), hypophosphatemia (75%), and thrombocytopenia (67%)
Five patients experienced cytokine release syndrome (CRS) of grades 1 (n=2), 2 (n=1), and 3 (n=2)
○ CRS occurred within a median of four days post-infusion (range 0-11 days; 1 instance occurred on day of treatment), and the median duration of CRS was ten days (range 8 – 28 days)
Another safety assessment was monitoring for lentivirus that is used for gene transfer during manufacturing. Polymerase chain reaction (PCR) was performed and all patients were found to be negative for replication-competent lentivirus.
Clonality assessment was carried out to exclude insertional oncogenesis as a mechanism for persistence, and all analyzed samples showed high levels of SPEAR T-cell polyclonality with the absence of dominant clones indicating that oncogenesis is not a mechanism of persistence
SPEAR T-cells expand significantly in responding patients with long-term persistence and functionality

SPEAR T-cells were detectable in all patients following infusion, with peak levels measured within the first ten days
Peak NY-ESO vector copy levels were statistically significantly higher (p = 0.0411) in responders compared to non-responders
Among seven patients for whom monitoring continued beyond 200 days, circulating SPEAR T-cells were readily detectable
Persisting pools comprised largely central memory and stem cell memory subsets that remained virtually negative for exhaustion markers such as PD-1 and LAG-3 for the duration of the analysis period (up to 6 months)
CD8+ SPEAR T-cells were isolated from the pre-infusion product and at post-infusion time points, and analyzed for cytokine production in an in vitro assay with NY-ESO expressing target cells; cytokine staining showed production of various cytokines by SPEAR T-cells in vitro (i.e., IFN-γ, IL-2, or TNF-α; or, combinations thereof) indicating that SPEAR T-cells are polyfunctional both pre- and post-infusion
SPEAR T-cells from patient 202 were isolated and placed in an in vitro killing assay 28 months after infusion and found to kill NY-ESO expressing target cells without addition of exogenous cytokines
Responses in a second solid tumor, myxoid/round cell liposarcoma (MRCLS) with NY-ESO SPEAR T-cells were recently reported, and these data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2, 2018.

On June 11, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY), reported that the United States Food and Drug Administration (FDA) has approved Venclexta (venetoclax) in combination with Rituxan (rituximab) for the treatment of people with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy (Press release, Hoffmann-La Roche, JUN 11, 2018, View Source [SID1234527254]). Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

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"We are pleased that this approval makes Venclexta, a first-of-its-kind targeted therapy, available for more people with chronic lymphocytic leukaemia whose disease has returned after previous treatment," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Venclexta plus Rituxan provides a new chemotherapy-free option shown to help people live longer without their disease progressing compared to a standard-of-care therapy."

The approval of Venclexta plus Rituxan for people with previously treated CLL is primarily based on the results of the phase III MURANO study, which were published online in the New England Journal of Medicine in March 2018 and presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2017. The results showed that a fixed duration of treatment with Venclexta plus Rituxan significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 81% compared with bendamustine plus Rituxan, a current standard of care (HR=0.19; 95% CI 0.13-0.28; p<0.0001).

The most common side effects of Venclexta in combination with Rituxan include low white blood cell count, diarrhoea,upper respiratory tract infection, cough, fatigue, and nausea.

Today’s FDA approval converts Venclexta’s accelerated approval to a full approval. The FDA has also updated the indication for Venclexta as a single agent, which is now approved for the treatment of people with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy. Venclexta was previously granted accelerated approval in April 2016 as a single agent for the treatment of people with CLL with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy.

The supplemental New Drug Application based on the MURANO data was granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. The FDA also previously granted Breakthrough Therapy Designation for Venclexta in combination with Rituxan for the treatment of relapsed or refractory CLL. Venclexta in combination with Rituxan is recommended in the National Comprehensive Cancer Network guidelines as a treatment option for previously treated CLL (Category 1, Preferred).

An application for a variation of the marketing authorisation based on the MURANO data has also been submitted to and validated by the European Medicines Agency (EMA). Additional submissions of the MURANO data to health authorities around the world are ongoing.

About the MURANO study
MURANO (NCT02005471) is a phase III open-label, international, multicentre, randomised study evaluating the efficacy and safety of Venclexta in combination with Rituxan compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukaemia (CLL) who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR) and complete response rate (with or without complete blood count recovery, CR/CRi).

At the time of analysis, median overall survival had not been reached in either arm after a median follow-up of 22.9 months.

Common Grade 3 or higher adverse reactions occurring at least 2 percent more frequently in patients treated with Venclexta plus Rituxan vs. BR, respectively, were low white blood cell count (neutropenia, 62% vs. 44%), diarrhoea (3% vs. 1%) and tumor lysis syndrome (3% vs. 1%).

About Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world.1 CLL mainly affects men and the median age at diagnosis is about 70 years.2 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.3

In CLL, the cancer primarily occurs in the blood and bone marrow. Small lymphocytic lymphoma (SLL) is similar to CLL, but primarily occurs in the lymph nodes.

About Venclexta
Venclexta is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). Overexpression of the BCL-2 protein in CLL has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signalling system that tells cells, including cancer cells, to self-destruct. Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie, under the brand name Venclyxto, outside of the United States.

Together, the companies are committed to further research with Venclexta, which is currently being evaluated in phase III clinical trials for the treatment of CLL, along with studies in several other types of cancers. In the United States, Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory CLL; as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

On June 8, 2018 Surface Oncology (NASDAQ:SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that Chief Executive Officer Jeff Goater will present at the Goldman Sachs 39th Annual Global Healthcare Conference in Rancho Palos Verdes, California on Wednesday, June 13th at 3:20 p.m. Pacific time (Press release, Surface Oncology, JUN 8, 2018, View Source [SID1234527442]).

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A live webcast of the discussion will be accessible through Surface Oncology’s Investor Relations website at investors.surfaceoncology.com. A replay of the webcast will be archived on Surface Oncology’s website for 30 days following the presentation.

On June 8, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has approved Venclexta (venetoclax) in combination with Rituxan (rituximab) for the treatment of people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy (Press release, Genentech, JUN 8, 2018, View Source [SID1234527253]). Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.

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

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"We are pleased that this approval makes Venclexta, a first-of-its-kind targeted therapy, available for more people with chronic lymphocytic leukemia whose disease has returned after previous treatment," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Venclexta plus Rituxan provides a new chemotherapy-free option shown to help people live longer without their disease progressing compared to a standard-of-care therapy."

The approval of Venclexta plus Rituxan for people with previously treated CLL is primarily based on the results of the Phase III MURANO study, which were published online in the New England Journal of Medicine in March 2018 and presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2017. The results showed that a fixed duration of treatment with Venclexta plus Rituxan significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 81 percent compared with bendamustine plus Rituxan, a current standard of care (HR=0.19; 95 percent CI 0.13-0.28; p<0.0001).

The most common side effects of Venclexta in combination with Rituxan include low white blood cell count, diarrhea, upper respiratory tract infection, cough, fatigue, and nausea.

Today’s FDA approval converts Venclexta’s accelerated approval to a full approval. The FDA has also updated the indication for Venclexta as a single agent, which is now approved for the treatment of people with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy. Venclexta was previously granted accelerated approval in April 2016 as a single agent for the treatment of people with CLL with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy.

The supplemental New Drug Application (sNDA) based on the MURANO data was granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. The FDA also previously granted Breakthrough Therapy Designation for Venclexta in combination with Rituxan for the treatment of relapsed or refractory CLL. Venclexta in combination with Rituxan is recommended in the National Comprehensive Cancer Network (NCCN) guidelines as a treatment option for previously treated CLL (Category 1, Preferred).

An application for a variation of the marketing authorization based on the MURANO data has also been submitted to and validated by the European Medicines Agency (EMA). Additional submissions of the MURANO data to health authorities around the world are ongoing.

About the MURANO study

MURANO (NCT02005471) is a Phase III open-label, international, multicenter, randomized study evaluating the efficacy and safety of Venclexta in combination with Rituxan compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukemia (CLL) who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR) and complete response rate (with or without complete blood count recovery, CR/CRi).

At the time of analysis, median overall survival had not been reached in either arm after a median follow-up of 22.9 months.

Common Grade 3 or higher adverse reactions occurring at least 2 percent more frequently in patients treated with Venclexta plus Rituxan vs. BR, respectively, were low white blood cell count (neutropenia, 62% vs. 44%), diarrhea (3% vs. 1%), and tumor lysis syndrome (3% vs. 1%).

About CLL/SLL

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, and in 2018, it is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.

In CLL, the cancer primarily occurs in the blood and bone marrow. Small lymphocytic lymphoma (SLL) is similar to CLL, but primarily occurs in the lymph nodes.

On June 8, 2018, Genocea Biosciences, Inc. updated its corporate presentation (Presentation, Genocea Biosciences, JUN 8, 2018, View Source [SID1234527249]).

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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

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