On December 9, 2019 Oncolytics Biotech Inc. (NASDAQ:ONCY)(TSX:ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, reported that a poster presentation was given over the weekend highlighting pre-clinical and clinical results of combining pelareorep with the proteasome inhibitor carfilzomib in the treatment of multiple myeloma (Press release, Oncolytics Biotech, DEC 9, 2019, View Source [SID1234552096]). The presentation was given on Saturday, December 7 as part of the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exhibition.

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The poster, titled, "Carfilzomib Impairs the Innate Antiviral Immune Response and promotes cytotoxic T-cell Expansion in Oncolytic Virus Treated Multiple Myeloma Patients" describes synergies between proteasome inhibitors and pelareorep concerning immune cell changes and response in myeloma patients.

"These findings demonstrate that pelareorep, in combination with carfilzomib, infects multiple myeloma cells, thereby providing a strong scientific rationale regarding immune cell changes," said Dr. Rita Laeufle, Chief Medical Officer at Oncolytics Biotech. "The combination of carfilzomib and pelareorep promotes expansion of killer T cells in patients on an ongoing phase 1b study and how it may lead to tumor response when pelareorep is combined with proteasome inhibitors. We are confident that pelareorep could add significant clinical value to the treatment of multiple myeloma patients with the combination of these agents. Our first data in patients from an ongoing study has been very encouraging and further data will be presented at subsequent clinical conferences."

Key data and conclusions:

Demonstrated that pelareorep treatment selectively infected multiple myeloma cells and not normal bone marrow cells
Carfilzomib enhances reovirus entry, infection, and killing of multiple myeloma cells
Reovirus significantly increases the frequency and activation of certain killer T cells, and increases the anti-tumor activity of immune cells in multiple myeloma
Data supports that the combination of pelareorep, and carfilzomib potentiates the expansion of CD8+ killer T cells
The poster presentation was authored by Dr. Flavia Pichiorri, Associate Professor in the Judy and Bernard Briskin Center for Multiple Myeloma Research within the Hematologic Malignancies and Stem Cell Transplantation Institute at the City of Hope, et al. The poster can be found on the Posters & Publications page of Oncolytics’ website, View Source

Title: Carfilzomib Impairs the Innate Antiviral Immune Response and promotes cytotoxic T-cell Expansion in Oncolytic Virus Treated Multiple Myeloma Patients

Number: 1816
Presenter: Dr. Flavia Pichiorri
Program: Oral and Poster Abstracts
Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster I

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

On December 9, 2019 FORMA Therapeutics, Inc., a clinical stage biopharmaceutical company focused on rare hematologic diseases and cancers, reported positive preliminary Phase 1/2 results from an ongoing study of olutasidenib, a next-generation inhibitor of mutated IDH1 (IDH1m), in patients with IDH1m acute myeloid leukemia (AML) and IDH1m myelodysplastic syndrome (MDS) (Press release, Forma Therapeutics, DEC 9, 2019, View Source [SID1234552117]). The data, presented at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper), demonstrate the potential of olutasidenib to induce rapid remissions and mutation clearance in a percentage of patients with IDH1m AML and MDS.

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"We are very pleased with the safety and clinical activity observed in this study of high-risk patients," said Patrick Kelly, M.D., chief medical officer of FORMA Therapeutics. "As we continue our Phase 2 evaluation, the therapeutic potential of olutasidenib to restore normal cellular differentiation in IDH1m malignancies, as well as to become a best-in-class treatment option, remains promising."

"In the U.S. alone, more than 20,000 new cases of AML are diagnosed each year, with about one-third of those evolving from patients with MDS," said Frank Lee, chief executive officer of FORMA Therapeutics. "Despite recent advances in the field, the low median five-year survival rate for AML patients is only 28%, so the need for a new therapy to transform patient outcomes remains significant."

FORMA is conducting a Phase 1/2 study evaluating the safety, efficacy and pharmacokinetics/pharmacodynamics (PK/PD) of olutasidenib for patients with AML or MDS with an IDH1 mutation. Phase 1 of the trial, 2102-HEM-101, was an open-label, dose-escalation and expansion study of olutasidenib alone and in combination with azacitidine (AZA). Phase 2 is an ongoing, open-label, fixed dose study of olutasidenib as a monotherapy and in combination with AZA in multiple IDH1m AML/MDS populations. Phase 2 includes a pivotal arm with olutasidenib as a monotherapy in relapsed and refractory (R/R) AML.

Presentation Overviews

Olutasidenib (FT-2102), an IDH1m Inhibitor as a Single Agent or in Combination with Azacitidine, Induces Deep Clinical Responses with Mutation Clearance in Patients with Acute Myeloid Leukemia Treated in a Phase 1 Dose Escalation and Expansion Study

Oral presentation by Justin Watts, MD, Assistant, Professor University of Miami, Sylvester Comprehensive Cancer Center

Results announced today are based on continuous oral treatment of olutasidenib for 28-day cycles, either alone (n=32) or in combination with AZA (n=46), in patients with IDH1m AML, with a dose evaluation of 300 mg once daily for olutasidenib alone and 150 mg once daily or twice daily for olutasidenib in combination with AZA. The findings indicate:

Olutasidenib is well tolerated as monotherapy and in combination with AZA;
No dose-limiting toxicities in dose escalation; 150 mg BID is the RP2D based on optimal exposure and robust 2-HG response;
Olutasidenib demonstrates clinical activity in a high-risk Phase 1 AML population; and
Olutasidenib induces IDH1 mutation clearance in a percentage of patients with TN and R/R AML regardless of IWG response.
FORMA’s Phase 2 study is ongoing with olutasidenib 150 mg BID as monotherapy and in combination with AZA in multiple IDH1m AML and MDS populations.

Olutasidenib (FT-2102) Induces Rapid Remissions in Patients with IDH1-Mutant Myelodysplastic Syndrome: Results of Phase 1/2 Single Agent Treatment and Combination with Azacitidine

Oral presentation by Jorge E. Cortes, MD, Professor, Augusta University, Director of the Georgia Cancer Center

Results presented today are based on continuous oral treatment of olutasidenib for 28-day cycles, either alone (n=6) or in combination with AZA (n=17) in 23 patients (16 relapsed/refractory, 7 treatment naïve) with IDH1m MDS. The findings indicate:

Olutasidenib is well-tolerated as a single agent and in combination with AZA;
Olutasidenib demonstrates preliminary clinical activity as a single agent and in combination with AZA in treatment-naive and relapsed/refractory patients with MDS;
Mutation clearance was observed in a percentage of evaluable patients; and
Rapid and sustained reduction of 2-HG was seen by the end of the first cycle.
About Olutasidenib (FT-2102)

FORMA Therapeutics’ most advanced clinical asset, olutasidenib, is designed to be a potent and selective next generation inhibitor of mutated isocitrate dehydrogenase 1 (IDH1m) to treat patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), as well as patients with glioma and other solid tumors with an IDH1 mutation. IDH1 is a natural enzyme that is part of the normal metabolism in all cells; when mutated, its activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 7-14% of patients with AML, 3-4% of patients with MDS, and more than 70% of patients with gliomas. In AML, hypermethylation driven by IDH mutations inhibits normal differentiation of progenitor cells leading to accumulation of immature blasts. Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed disease remain an unmet need. In MDS, often a precursor to AML, epigenetic changes from aberrant DNA methylation contribute to the formation of blast cells and the progression of MDS to AML.

On December 9, 2019 Immunocore Limited, a leading T Cell Receptor (TCR) biotechnology company, reported the start of the first-in-human clinical trial of IMC-C103C, the third bispecific developed using the company’s innovative ImmTAC technology platform (Press release, Immunocore, DEC 9, 2019, View Source [SID1234552134]). IMC-C103C is focused on targeting tumours that express the protein MAGE-A4 (Melanoma-Associated Antigen A4) and is being developed in partnership with Genentech, a member of the Roche Group.

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The trial (IMC-C103C-101) is designed to study the safety and preliminary activity of IMC-C103C as a monotherapy and in combination with atezolizumab (Tecentriq) in patients with MAGE-A4-expressing cancers.

David Berman, Head of Research and Development at Immunocore, commented: "We have now brought our third TCR- engineered bispecific ImmTAC into the clinic. IMC-C103C is designed to re-direct T cells to attack MAGE-A4 expressing tumours and we’re pleased to be moving its clinical development forward in partnership with Genentech."

On December 9, 2019 CStone Pharmaceuticals ("CStone" or the "Company", HKEX: 2616) reported that results from the CS1001-201 trial in a poster presentation at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, CStone Pharmaceauticals, DEC 9, 2019, View Source [SID1234552151]).

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CS1001-201 trial is a single-arm, multicenter Phase II clinical study designed to evaluate CS1001 monotherapy in relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (rr-ENKTL).

ENKTL is a subtype of mature T cell and NK cell lymphoma. It has a higher incidence in Asia than in Europe or North America. ENKTL is characterized by its rapid progression and poor prognosis. Currently, patients with rr-ENKTL lack effective treatment after failing an L-asparaginase-based combination chemotherapy regimen and targeted monotherapy only produces a complete response (CR) rate of below 10%.

"ENKTL accounts for approximately 6% of all lymphoma incidences, and there are vast unmet medical needs in this patient population that has failed the first-line treatment," said Dr. Frank Jiang, Chief Executive Officer and Chairman of CStone. "The CS1001-201 trial is the first clinical study of an anti-PD-L1 antibody in ENKTL worldwide. Our latest data have shown CS1001 to be well-tolerated with preliminary antitumor efficacy and survival benefit in rr-ENKTL patients. We will continue to advance this development program and hope that CS1001 will soon become a new treatment option for rr-ENKTL patients."

"CR is a critical outcome measure for the treatment of ENKTL. Studies have shown that ENKTL patients who achieved CR prior to autologous transplantations have a significantly better prognosis and longer survival than those who achieved partial response," said Dr. Jason Yang, Chief Medical Officer of CStone. "These latest results of CS1001 demonstrated a CR rate of 33.3% with durable response, an objective response rate of 43.3%, and a 1-year overall survival rate of 72.4%. These results represent a major breakthrough compared to current treatment options and support CS1001 as a potential conditioning regimen for hematopoietic stem cell transplantations."

Overview of the CS1001-201 trial

CS1001-201 is a single-arm, multicenter Phase II clinical study designed to evaluate CS1001 monotherapy in relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (rr-ENKTL).

The primary endpoint of the trial is ORR assessed by an independent radiological review committee (IRRC);
Secondary endpoints include investigator-assessed ORR; IRRC-assessed CR and PR rates, time to response, duration of response, progression-free survival; overall survival, and safety.
Results reported in the poster at the 2019 ASH (Free ASH Whitepaper) Annual Meeting

As of October 8, 2019, 32 patients were enrolled in the study. Among them, 24 patients (75.0%) had Stage IV ENKTL at screening, 9 patients (28.1%) received 2 lines of prior treatments, and 7 patients (21.9%) received 3 or more lines of prior treatments. All patients received 1200 mg CS1001 intravenously every 3 weeks for up to 2 years, until disease progression, intolerance, etc. The median duration of follow-up was 6.54 months (range, 0.72-15.64).

13 (40.6%) of the 32 enrolled patients remained on treatment, and 19 (59.4%) had discontinued from the study treatment.
Reasons for discontinuations included radiographic disease progression (12 patients), adverse events (AEs, 4 patients), and non-radiographic symptomatic progression (3 patients).
No deaths due to treatment-related AEs (TRAEs).
Preliminary efficacy data

CS1001 demonstrated promising antitumor activity and a favorable CR rate with durable response and survival benefit in rr-ENKTL patients.

Among the 30 efficacy-evaluable patients, the investigator-assessed ORR was 43.3%.
10 patients (33.3%) achieved CR and were still in remission.
3 patients (10.0%) achieved partial response (PR), and 1 additional patient achieved PR after pseudo-progression. The median duration of response (DoR) was not reached, and the maximum DoR was 10.9+ months.
The 1-year overall survival (OS) was 72.4% (95% CI: 52.0%-85.2%).
The IRRC assessments were not available at the time of data cut-off.
Safety data

CS1001 was well tolerated in patients with rr-ENKTL

The median duration of treatment was 12.6 weeks (range, 3.0-69.1).
30 patients (93.8%) reported treatment-emergent AEs (TEAEs).
24 patients (75.0%) reported TRAEs, of which 3 (9.4%) had Grade >3 TRAEs.
Grade 5 AEs were reported in 3 patients (9.4%), and none was assessed as related to CS1001.
7 patients (21.9%) reported serious AEs (SAEs). 1 case of Grade 4 sinus node dysfunction and 1 case of Grade 1 myositis were assessed as related to CS1001 by the investigator. Both patients later recovered from the SAEs.
Immune-related AEs (irAEs) were reported in 5 patients (15.6%). Except for 1 Grade 3 rash, all irAEs were Grade 1 in severity.
TEAEs that led to permanent treatment discontinuation occurred in 4 patients (12.5%).
No deaths due to AEs were assessed as related to CS1001.
About CS1001

CS1001 is an investigational monoclonal antibody directed against PD-L1 being developed by CStone. Authorized by the U.S. based Ligand Corporation, CS1001 is developed by the OMT transgenic animal platform, which can generate fully human antibodies in one step. As a fully human, full-length anti-PD-L1 monoclonal antibody, CS1001 is similar to natural G-type immune globulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities, potentially representing a unique advantage over similar drugs.

CS1001 has completed a Phase I dose-escalation study in China, in which CS1001 showed good tolerability and produced sustained clinical benefits during the Phase Ia study.

CS1001 is being investigated in a number of ongoing clinical trials, including one Phase I bridging study in the U.S. In China, its clinical program includes one multi-arm Phase Ib study, two pivotal Phase II studies, and three Phase III studies for several tumor types.

On December 9, 2019 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics to treat cancer, reported further progress on key elements of its ongoing Phase 1/2 clinical trial entitled "A Phase 1/2 Study in Patients with Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions" (ClinicalTrials.gov Identifier: NCT03947385) (Press release, Ideaya Biosciences, DEC 9, 2019, View Source [SID1234552167]). This clinical trial is evaluating the tolerability and preliminary clinical activity of IDE196 for the treatment of Metastatic Uveal Melanoma (MUM) and other solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations activating the PKC signaling pathway.

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"The pharmacokinetic clinical sub-study for the tablet formulation is on-track to start in January 2020. This may enable the initiation of the Phase 2 expansion to coincide with potential introduction of the tablet in Q1 2020. We also continue to evaluate the Phase 1 dose escalation data, including pharmacokinetic and tolerability data, as we target to advance IDE196 into the potentially registration-enabling study for MUM," said Julie Hambleton, M.D., Chief Medical Officer and Senior Vice President at IDEAYA Biosciences.

Key updates include:

Initiated 13-week GLP-compliant toxicology studies in 2 species in November 2019, in support of registration-enabling FDA requirement to submit study results prior to enrollment of more than approximately 50 patients in the investigational arm of the clinical trial that will support a marketing application
Pharmacokinetic Phase 1 clinical sub-study with immediate release tablet formulation of IDE196 scheduled to initiate in January 2020, in support of potential introduction of the tablet in the Phase 2 clinical trial in Q1 2020
Targeting initiation of Phase 2 single-arm potentially registration-enabling clinical trial in MUM in Q1 2020, which we anticipate may coincide with introduction of tablet formulation
Targeting initiation of combination clinical trial of IDE196 plus a MEK inhibitor in H1 2020, accelerated from earlier guidance. Preclinical evaluation of potential additional combinations ongoing
Total of 40 patients enrolled in the Phase 1 portion of the Phase 1/2 GNAQ/11 basket trial as of as of December 6, 2019, including 38 MUM patients, for which dose escalation is complete, and 2 non-MUM patients, for which enrollment is ongoing
Launching the IDEAYA Genomics Profiling Initiative (IDEAYA GPI). IDEAYA GPI is a company initiative leveraging various Next Generation Sequencing (NGS) platforms, including in partnership, to identify patients having tumors with specific mutations, such as tumors with activating GNAQ/11 mutations for potential enrollment in our IDE196 basket trial
On track to present interim clinical data from the GNAQ/11 Phase 1/2 monotherapy basket trial in Q2/Q3 2020
"We are excited for the opportunity to initiate the single-arm Phase 2 monotherapy expansion, which is potentially registration-enabling for MUM. We also look forward to advancing the clinical combination of IDE196 with MEK, as well as the GNAQ/11 basket trial to evaluate the clinical activity of IDE196 in non-MUM patients, including in skin melanoma," said Yujiro S. Hata, Chief Executive Officer and President at IDEAYA Biosciences.