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Checkmate Pharmaceuticals Presents Positive Clinical Data with CMP-001 at The 34th Annual Meeting of The Society for Immunotherapy of Cancer (SITC)

On November 5, 2019 Checkmate Pharmaceuticals Inc. (Checkmate), a clinical stage biopharmaceutical company focused upon activation of innate immunity to treat cancer, reported the presentation of new data from two ongoing clinical trials evaluating CMP-001, Checkmate’s Toll-like receptor 9 (TLR9) agonist, in combination with the anti-PD-1 therapies pembrolizumab (KEYTRUDA) or nivolumab (OPDIVO), in patients with melanoma (Press release, Checkmate Pharmaceuticals, NOV 5, 2019, View Source [SID1234550365]).

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"CMP-001 is a differentiated TLR9 agonist that activates a tumor-specific T cell response. When combined with checkpoint inhibitors, CMP-001 can induce deep and durable systemic anti-tumor responses," said Dr. Art Krieg, Checkmate’s Founder and CSO. "These clinical data reaffirm the potential for CMP-001 to enhance responsiveness or overcome resistance to immune checkpoint inhibitors. We look forward to the next stages of development with this program, including evaluation in other cancers."

Durable responses in anti-PD-1 refractory melanoma following intra-tumoral injection of a Toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab (Abstract #: 11548/O87)

On Friday, November 8, 2019 at 12:15pm ET, Dr. John M. Kirkwood, Usher Professor of Medicine and Dermatology, University of Pittsburgh School of Medicine, and Co-Director, Melanoma and Skin Cancer Program, University of Pittsburgh Cancer Institute and UPMC Hillman Cancer Center, is presenting late-breaking data from a Checkmate-sponsored clinical trial of CMP-001, either in combination with pembrolizumab or as monotherapy (NCT02680184).

Updated data from the trial demonstrated that the combination of CMP-001 and pembrolizumab continued to be well tolerated, with an objective response rate (ORR) of 25% according to RECIST v1.1 criteria. The study treatment induced deep and durable systemic anti-tumor responses in patients with melanoma who previously progressed on anti-PD-1 treatments; with a current Kaplan Meier estimate of median duration of response of 16.9+ months for the 28 RECIST v1.1 responders.

"These current data suggest that CMP-001 might expand the patient population that benefits from anti-PD-1 therapies," said Dr. Kirkwood. "Most patients with cancer have non-inflamed tumor microenvironments that do not respond to checkpoint inhibitors. These trial data demonstrate that combining CMP-001 with pembrolizumab could induce an immune response against the cancer, forming a potentially effective treatment option for patients with advanced melanoma who are not responsive to anti-PD-1-based treatment regimens."

Data were presented on the intent to treat (ITT) population of 144 patients receiving combination therapy with CMP-001 and pembrolizumab. Two formulations of CMP-001 were evaluated, either 0.01% polysorbate 20 (PS20, N=83) or 0.00167% PS20 (N=61). The lower concentration of PS20 was found to be less effective. Data were also presented on 24 patients who received CMP-001 monotherapy.

Key highlights from these clinical data include:

CMP-001 in combination with pembrolizumab

The RECIST ORR in patients who received the 0.01% PS20 formulation was 25% (21/83; 95% confidence interval 16%-36%), including 6 complete responses and 15 partial responses.
Four additional patients who continued study therapy beyond initial disease progression achieved a partial or complete response.
The Kaplan Meier estimate for median duration of response is 16.9+ months [95% CI=5.8, not reached] in the 28 RECIST responders and 25.2+ months [95% CI=8.6, not reached] when including the additional 4 patients with post-progression responses. The median duration of response has not been reached.
Among responding patients, non-injected target lesions regressed by a similar magnitude to injected target lesions.
In the ITT population, the most common treatment-related adverse events were flu-like symptoms, including chills, fever, fatigue, nausea, vomiting and headache for patients receiving combination treatment. Six patients (4%) discontinued study therapy due to treatment-related adverse events.
CMP-001 monotherapy

Of the 24 patients treated with CMP-001 monotherapy, 5 patients achieved a partial response. Responses were less durable compared to those for patients receiving CMP-001 in combination with pembrolizumab.
Phase II Trial of neoadjuvant nivolumab (Nivo) and intra-tumoral (IT) CMP-001 in high risk resectable melanoma (MEL): Preliminary Results (Abstract #: 11648/O34)

On Saturday, November 9, 2019 at 6:15pm ET, Dr. Diwakar Davar, Assistant Professor of Medicine at the University of Pittsburgh School of Medicine, is presenting data from an investigator-sponsored trial evaluating neoadjuvant treatment with CMP-001 in combination with nivolumab in patients with Stage IIIB/C/D Melanoma (NCT03618641).

Preliminary data from the trial show that neoadjuvant IT CMP-001 in combination with nivolumab in PD-1 naïve patients was generally well tolerated with no dose limiting toxicities or delays in surgery related to the neoadjuvant treatment. A major pathologic response rate (MPR) of 71% (15/21) was reported in 21 evaluable patients to date. Of the 15 responding patients, 13 patients had a pathological complete response (pCR). These data suggest that the addition of IT CMP-001 may increase the clinical efficacy of PD-1 blockade. Furthermore, translational studies demonstrated that the combination augmented peripheral blood and intra-tumoral anti-melanoma CD8+ T cell immune responses.

"The preliminary results of our study show that a combination treatment with neoadjuvant nivolumab and CMP-001 is associated with high rates of major pathologic response, including a remarkable proportion of subjects with complete pathological response," said Dr. Davar. "Moreover, the combination treatment has a favorable toxicity profile. We look forward to evaluating the effect of the treatment upon post-surgical relapse as the data mature."

About Checkmate’s Phase 1b Study (CMP-001-001)

CMP-001-001 (NCT02680184) is an ongoing, multicenter two-part, open label Phase 1b clinical study in advanced melanoma. The study is being conducted at 13 sites in the USA.

The primary objective of Part 1 of the study is to determine the recommended phase 2 dose (RP2D) of CMP-001 when given in combination with pembrolizumab in PD-1 resistant patients. Secondary objectives are to assess the safety and efficacy of CMP-001 when given in combination with pembrolizumab, and to assess the pharmacodynamic effects of the addition of CMP-001 to pembrolizumab on serum concentrations of CXCL10 (IP-10).

Part 1 of the study utilized a dose escalation scheme to identify the RP2D and schedule. During dose escalation, patients were enrolled to cohorts of ≥ 3 patients at CMP-001 doses of 1, 3, 5, 7.5, and 10 mg CMP-001 in two dosing schedules (weekly for 7w, followed by q3w; or weekly for 2w, followed by q3w).

In the Part 1 dose expansion, two formulations of CMP-001 were evaluated, either with 0.01% polysorbate (PS20) or with 0.00167% PS20. The CMP-001 0.01% PS20 formulation, 10 mg dose, with a weekly dosing schedule for 7w, followed by q3w dosing, was selected for further development.

Part 2 of the study continues to enroll and is evaluating the safety and efficacy of CMP-001 administered as monotherapy at the same dose, schedule and formulation selected for further development in Part 1 of the study.

About CMP-001

CMP‐001 is a first‐in‐class CpG‐A Toll‐like receptor 9 (TLR9) agonist that is encapsulated in a virus‐like particle. CMP‐001 is designed to induce both innate and adaptive anti‐tumor immune responses, thereby converting immunologically "cold" tumors into immunologically "hot" tumors, with the potential to mediate tumor regression. It is the only CpG‐A class TLR9 agonist in clinical trials and differs from other CpG classes in clinical development by having a native DNA backbone that induces the highest levels of type I Interferon (IFN). Based on analyses of gene expression in human tumors showing that increased IFN and related immune gene expression is associated with better response to PD‐1 inhibition, it is believed that this mechanism of action may restore, enable or improve responses to anti‐PD‐1/PD‐L1 therapeutics. CMP‐001 is being evaluated in multiple tumor types to assess safety, activity, alternative routes of administration and combination with other immunotherapies and modalities. For information on CMP‐001 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

Senti Biosciences Announces Upcoming Presentation of SENTI-101 Preclinical Efficacy Data at SITC 2019

On November 5, 2019 Senti Biosciences, the gene circuit company focused on outsmarting complex diseases with intelligent medicines, reported that Senti scientists will present data at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held November 6-10, 2019, in National Harbor, Maryland (Press release, Senti Biosciences, NOV 5, 2019, View Source [SID1234550364]).

Senti’s gene circuit platform enables the programming of any cell and gene therapy modality, including immune cells, stem cells, and viral vectors. The poster presentation highlights preclinical data from one of Senti’s programs, SENTI-101, an allogeneic cell therapy designed to treat patients with ovarian cancer and other solid tumors.

"This SITC (Free SITC Whitepaper) poster presentation is an important milestone for Senti Biosciences because it reveals an exciting translational application of our gene circuit platform, which has the potential to broadly transform cell and gene therapies," said Dr. Timothy Lu, CEO of Senti Biosciences.

The SENTI-101 program uses tumor-homing allogeneic cells as a drug delivery vehicle to achieve localized, combinatorial expression of two cytokines. This pair of cytokines activates a multifactorial immune response against solid tumors, and turns immunologically cold tumors hot. SENTI-101 was developed through Senti’s systematic design-build-test-learn process, wherein more than 250 different gene circuits including individual, two-wise and three-wise combinations of immune effectors were tested for their ability to treat cold tumors and trigger a robust tumor immunity cycle. This approach of programming artificial pharmacology into allogeneic cells enables delivery of high concentrations of multi-factorial immunotherapies locally in the tumor microenvironment, which Senti believes will be critical to transforming therapy for solid tumors.

"There’s a huge unmet need when it comes to developing treatments for patients whose tumors do not respond to checkpoint inhibitors, and we are excited about the potential for SENTI-101 to help these patients," said Gary Lee, Ph.D., Chief Scientific Officer at Senti Biosciences.

SENTI-101 is a novel product candidate comprising allogeneic mesenchymal stromal cells (MSCs) genetically modified to express a combination of immunomodulatory cytokines — Interleukin 12 (IL-12) and Interleukin 21 (IL-21). Together, IL-12 and IL-21 enable highly effective and complementary stimulation of anti-tumor immunity.

Upon administration in preclinical models, SENTI-101:

Innately homes to peritoneal tumors (>10-fold higher vs. normal tissues, p≤0.0001)
Secretes IL-12 and IL-21 in a localized and sustained fashion within tumors of the peritoneal space (~100-fold greater in peritoneal space vs. serum [p≤0.002])
Induces a robust and durable anti-tumor immune response, resulting in more than 200-fold (p≤0.0001) and 10-fold (p≤0.0001) reduction in tumor burden in CT26-fLUC and B16-F10-fLUC models, respectively
Prolongs tumor-free survival compared to controls and checkpoint inhibitor therapy in syngeneic tumor models, including the checkpoint refractory B16-F10 model, and notably, mice treated with the SENTI-101 combination outperformed those treated with MSCs expressing each individual cytokine
Additionally, surviving mice rejected a second round of newly implanted tumor cells, thereby demonstrating anti-tumor immune memory
Mechanistically involves multiple important immune cell subtypes, including CD4 and CD8 T cells, antigen-presenting cells (APCs), B cells and NK cells
The SITC (Free SITC Whitepaper) abstract can be accessed here: http://bit.ly/2Wt2wli

Recent Corporate Update

In addition to its gene circuits and translational biology capabilities, Senti has established in-house process development, regulatory, and clinical expertise to pursue IND-enabling studies, GMP manufacturing, and clinical protocol development for its pipeline. Additional gene circuit cell therapy programs for solid tumors and difficult-to-treat liquid tumors are also underway, with plans to advance candidates for clinical development in the next year.

Senti’s corporate strategy is focused on internal product development, as well as establishing collaborations with other companies. The gene circuit platform can be paired with a variety of complementary technologies to create next-generation cell and gene therapies with improved performance. For example, Senti’s engineered promoters and logic gates enable cell and gene therapies with programmable specificity and high activity in defined cell states or cell types. In addition, Senti’s Pro-Dial platform allows for cell and gene therapies to be titrated up or down in a rheostat fashion with FDA-approved small molecule drugs. These technologies have the potential to make cell and gene therapies controllable, targeted and dynamic, thus increasing the therapeutic window and addressing indications not accessible by current therapies.

IONpath Announces Commercial Launch of MIBIscope™—the First Multiplexed Ion Beam Imaging System

On November 5, 2019 IONpath, Inc., a company revolutionizing multiplexed tissue imaging, reported that launched the MIBIscope System, the first commercially available Multiplexed Ion Beam Imaging (MIBI) system (Press release, IONpath, NOV 5, 2019, View Source [SID1234550363]). The MIBIscope enables researchers to image over 40 biomarkers simultaneously at higher sensitivity, resolution, and throughput than existing methods. IONpath is showcasing the platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Maryland from November 6-10.

To help scientists see deeper into the tissue microenvironment and study the relationships between proteins, cells and their environment in intact tissue samples, IONpath has leveraged secondary ion mass spectrometry and elementally labeled antibodies to create MIBI technology. This method enables higher throughput than existing multiplexed imaging technologies, such as mass cytometry, and is far more sensitive, permitting single-molecule detection. The MIBIscope can image cellular structures as small as 280 nm and visualize over 40 biomarkers simultaneously with a dynamic range of five orders of magnitude.

"Scientists in oncology and translational research will benefit from the unprecedented insights into spatial relationships within the tissue microenvironment by imaging and characterizing tissue samples at subcellular resolution," said Harris Fienberg, chief executive officer and co-founder, IONpath. "After successfully piloting the MIBIscope in leading research and biopharma institutions, we are excited to bring the platform to market."

The MIBIscope System removes only a thin layer of sample during imaging, thus permitting scientists to perform multiple scans on a single sample. Further, by scanning at different levels of depth, researchers can study tissue architecture in three dimensions. The MIBIscope System can be automated to image tissue samples continuously for multiple days, allowing researchers to process hundreds of samples a week and conduct broad cohort studies.

The simple staining process employs a standard immunohistochemistry workflow and is compatible with both FFPE and fresh/frozen tissue. Furthermore, samples are stable for months following staining.

To learn about the MIBIscope, visit IONpath at SITC (Free SITC Whitepaper) booth #326, or attend the company’s symposium on Saturday, November 9 at 12:35 pm in Riverview Ballroom A3, where leading researchers from the Dana-Farber Cancer Institute, Stanford University, and University of Colorado, Denver, will be presenting their research using the MIBIscope to characterize the tumor microenvironment. More information about IONpath’s activities at SITC (Free SITC Whitepaper) can be found at View Source Information about the MIBIscope System can be found at View Source

PureTech Announces Presentation of New Data Supporting Wholly Owned Immuno-Oncology Programs LYT-200 (anti-galectin-9) and LYT-210 (anti-delta-1)

On November 5, 2019 PureTech Health plc (LSE: PRTC) ("PureTech"), a clinical-stage biotechnology company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the presentation of new preclinical data from its wholly-owned immuno-oncology programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting in National Harbor, Md (Press release, PureTech Health, NOV 5, 2019, View Source [SID1234550362]).

The two scientific posters detail the Company’s continued progress in advancing two fully human monoclonal antibodies (mAbs) developed to inhibit two foundational immunosuppressive orchestrators, galectin-9 (LYT-200) and pathogenic gamma delta-1 (γδ1) T cells (LYT-210).

"These data further show the unique position and importance of galectin-9 and γδ1 as immunosuppressors in cancer biology. Both have been observed to have powerful properties to disable immune-mediated cancer attack, which may explain some of the fundamental efficacy limitations of other immuno-oncology therapies," said Joseph Bolen, PhD, chief scientific officer at PureTech. "Our novel antibodies targeting galectin-9 and γδ1 have produced compelling single-agent preclinical data against a number of difficult-to-treat cancers in models where approved immunotherapies haven’t worked. We are excited to share our continued progress with the scientific community at premier conferences such as SITC (Free SITC Whitepaper)."

The new data presented at SITC (Free SITC Whitepaper) indicate that galectin-9 is not only a potent therapeutic target, but also a potentially relevant biomarker. Across multiple cohorts, galectin-9 was significantly increased in blood samples of individuals with primary and metastatic pancreatic cancer, lung tumors, and colorectal carcinoma, compared to healthy individuals.

"These findings validate the importance of galectin-9 in cancer biology and its potency as a target," said George Miller, MD, Director of S. Arthur Localio Laboratories and Director of the Cancer Immunology Program at NYU School of Medicine and a PureTech collaborator. "Our research indicates that galectin-9 is a master immunosuppressor; it induces a highly favorable microenvironment for tumor growth. LYT-200 has potential both as a single agent and in combination with checkpoint inhibitors to have therapeutic potential by reversing the immunosuppression which can be present in the tumor microenvironment."

PureTech expects to file an Investigational New Drug application (IND) for LYT-200 in the first half of 2020 and to initiate a Phase 1a/1b clinical trial in solid tumors in 2020. The mAb has been tested as a single agent as well as in combination with anti-PD1 checkpoint inhibitors in preclinical murine and human-derived ex vivo models, showing robust and reproducible activity, immune activation potential as well as excellent drug properties.

PureTech also presented data on its monoclonal antibody LYT-210 that targets γδ1 T cells whose immunosuppressive features leads to a tumor permissive microenvironment. The research presented at SITC (Free SITC Whitepaper) showed that γδ1 T cells were the most abundant T cell within the studied tumors, which included pancreatic, colorectal, cholangiocarcinoma, and liver cancer, and represented up to 50% of all infiltrating T cells. PureTech also presented data showing that LYT-210 depletes immunosuppressive γδ1 T cells through cytotoxicity and phagocytosis. Together, these findings further support the ability of LYT-210 to potentially restore the immune system’s ability to fight difficult-to-treat cancers. PureTech expects to file an IND for LYT-210 in 2021 for solid tumors.

"These data show that γδ1 cells play a key role in suppressing the immune system’s ability to attack tumors. LYT-210 is designed to remove and destroy pathogenic γδ1 T cells enabling immune mediated cancer attack. We therefore believe LYT-210 holds significant promise as a potential immunotherapy," said Dr. Miller.

Rocket Pharmaceuticals Announces Participation at the Barclays Gene Editing & Gene Therapy Summit

On November 5, 2019 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) ("Rocket"), a leading U.S.-based multi-platform clinical-stage gene therapy company, reported that Gaurav Shah, M.D., Chief Executive Officer and President of Rocket is scheduled to present on Wednesday, November 13, 2019, at 2:15 p.m. Eastern Time at the Barclays Gene Editing & Gene Therapy Summit, New York, N.Y (Press release, Rocket Pharmaceuticals, NOV 5, 2019, View Source [SID1234550361]).