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Mateon Therapeutics Announces New Interim Preclinical Data on CA4P in Combination with Checkpoint Inhibitors

On June 28, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that CA4P in combination with a checkpoint inhibitor significantly reduced tumor size in a CT-26 colon cancer animal model (Press release, Mateon Therapeutics, JUN 28, 2017, View Source [SID1234519707]).

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Mateon evaluated its lead investigational drug CA4P, which is also currently being studied in a phase 2/3 clinical trial in platinum-resistant ovarian cancer, in a syngeneic mouse model in combination with a checkpoint inhibitor. In order to assess the effects of CA4P on more advanced and difficult-to-treat tumors, tumors in this study were allowed to grow for 13 days prior to treatment. Consequently, beginning tumor sizes were approximately three times larger than those generally evaluated in preclinical studies. Results following two weeks of treatment are as follows:

Treatment Baseline
Tumor Size Day 14
Tumor Size Day 14 Survival Survival
p-values
Vehicle 159 mm3 2005 mm3 0 / 8 Not applicable
CA4P 159 mm3 1265 mm3 2 / 8 Not significant
Anti-CTLA-4 156 mm3 1016 mm3 4 / 8 0.048
CA4P + Anti-CTLA-4 157 mm3 229 mm3 8 / 8 0.001 *
* p=0.032, Anti-CTLA-4 vs. CA4P and anti-CTLA-4

"CA4P increases the effects of checkpoint inhibitors because it rapidly causes tumor cell death, which likely increases tumor antigen presentation and T-cell activation and the overall immunologic response," said William D. Schwieterman, M.D., President and Chief Executive Officer. "These new results reinforce similar results observed in other studies and, importantly, the animals in the combination CA4P and anti-CTLA-4 antibody treatment group are continuing to show declines in tumor volume beyond Day 14. We look forward to additional data from this study and other on-going preclinical work over the next several months."

Mean Tumor Volume in CT-26 Colorectal Mouse Model
Mean Tumor Volume in CT-26 Colorectal Mouse Model

An infographic accompanying this announcement is available at View Source
This is the second study and tumor type to demonstrate robust complementary effects when Mateon’s CA4P is provided in combination with a checkpoint inhibitor; results obtained approximately four months ago in a smaller tumor EMT-6 mammary model also showed strong synergy when anti-CTLA-4 antibodies were combined with CA4P.

Halozyme Phase 2 Data In Advanced Pancreas Cancer Presented At European Society For Medical Oncology Symposium

On June 28, 2017 Halozyme Therapeutics (NASDAQ: HALO) reported that Phase 2 randomized, multi-center clinical trial in pancreas cancer patients were shared today in two oral presentations at the European Society for Medical Oncology’s 19th World Congress on Gastrointestinal Cancer (Press release, Halozyme, JUN 28, 2017, View Source [SID1234519706]).

The HALO-202 study represents the first clinical trial of a molecularly targeted drug in pancreatic ductal adenocarcinoma and the results support hyaluronan (HA) as a potential biomarker to predict those patients who could benefit from Halozyme’s investigational new drug PEGPH20 (pegvorhyaluronidase alfa) when added to standard chemotherapy.

As previously reported, the study met its primary efficacy and safety endpoints and the key secondary endpoint of progression-free survival (PFS) in HA-High patients. PEGPH20 plus standard chemotherapy of ABRAXANE (nab-paclitaxel) and gemcitabine improved median PFS by 77 percent over chemotherapy alone in HA-High patients.

Dr. Andrew Hendifar, the medical oncology lead for the Gastrointestinal Disease Research Group at Cedars-Sinai and co-director of Pancreas Oncology delivered the presentation, "PEGPH20 Improves PFS in Patients With Metastatic Pancreatic Ductal Adenocarcinoma: A Randomized Phase 2 Study in Combination With nab-Paclitaxel/Gemcitabine."

Dr. Andrea Bullock, attending physician in Gastrointestinal Oncology at Beth Israel Deaconess Medical Center and an Instructor in Medicine at Harvard University delivered the presentation, "Tumor Hyaluronan May Predict Benefit From PEGPH20 When Added to nab-Paclitaxel/Gemcitabine in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma (mPDA)."

New safety data reported today show bleeding events were balanced between the two arms after the introduction of low molecular weight heparin in stage 2 of the study.

"The results of HALO-202 are encouraging and continue to support our ongoing HALO-301 phase 3 study in HA-High pancreas cancer patients," said Dr. Helen Torley, president and chief executive officer. "HALO-301 is now open for screening and enrollment at more than 200 centers in over 20 countries."

In addition to the oral presentations, Halozyme and its investigators are presenting three posters pertaining to the study of PEGPH20, including:

Musculoskeletal Adverse Events with PEGPH20 Treatment and Management in Patients with Previously Untreated Metastatic PDA (HALO-202), presented by Dr. Bullock;
Global, Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of PEGPH20 + nab-Paclitaxel & Gemcitabine in Pts with Previously Untreated, HA-High, Stage IV PDA (HALO-301), presented by Dr. E. Von Cutsem, a principal investigator in the study; and
A Systematic Review Examining the Relationship Between PFS and OS Survival In Adults With Untreated Metastatic Pancreatic Cancer, presented by Halozyme.
Pancreas cancer is the third-leading cause of cancer related death in the United States, and more than 65,000 people in the U.S. and top five European countries are diagnosed annually with advanced cases of the disease.

About HALO-301 and HALO-202
HALO-301 is a phase 3 global, randomized, double-blind placebo controlled clinical trial evaluating investigational new drug PEGPH20 as a first-line therapy for potential treatment of patients with metastatic pancreas cancer. The trial will be conducted at approximately 200 sites with two primary endpoints, progression free survival and overall survival in patients receiving investigational new drug PEGPH20 in combination with gemcitabine and ABRAXANE (nab-paclitaxel) compared to gemcitabine and nab-paclitaxel alone. Secondary endpoints also include objective response rate and overall survival. More information may be found at clinicaltrials.gov (search HALO 301 or trial identifier NCT02715804) or www.HALO301.com.

HALO-202 (Halo 109-202) is a phase 2 multi-center, randomized clinical trial evaluating investigational new drug PEGPH20 as a first-line therapy for potential treatment of patients with metastatic pancreas cancer. The primary outcome of the trial is to measure improvement in progression-free survival in patients receiving investigational new drug PEGPH20 in combination with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel alone. A second primary endpoint assesses the thromboembolic event rate in the PEGPH20 treatment arm. Secondary endpoints also include objective response rate and overall survival.

About PEGPH20 (pegvorhyaluronidase alfa)
PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan. PEGPH20 is an enzyme that temporarily degrades HA, a dense component of the tumor microenvironment that can accumulate in higher concentrations around certain cancer cells, potentially constricting blood vessels and impeding the access of other therapies.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreas cancer and fast track designation for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreas cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreas cancer.

CytomX Announces the First Patient Treated in Phase 1/2 PROCLAIM-CX-2009 Trial

On June 28, 2017 CytomX Therapeutics, Inc. (Nasdaq:CTMX), a biopharmaceutical company developing investigational Probody therapeutics for the treatment of cancer, reported the treatment of the first patient in the PROCLAIM-CX-2009 study (Probody Clinical Assessment In Man), a Phase 1/2 clinical trial evaluating CX-2009 as monotherapy in patients with select advanced solid tumors (Press release, CytomX Therapeutics, JUN 28, 2017, View Source [SID1234519705]). CX-2009 is a Probody drug conjugate (PDC) that targets CD-166, an antigen that is broadly and highly expressed in many types of cancers and is the first PDC to enter the clinic.

"The unique targeting ability of our Probody platform allows us to pursue targets not accessible to conventional antibody drug conjugates. With CX-2009, we are leveraging the high levels of CD-166 on many types of cancer cells despite its presence on normal tissue," said Sean McCarthy, D.Phil., president and chief executive officer of CytomX Therapeutics. "By targeting CD-166 and localizing the activity of the CX-2009 Probody therapeutic to the tumor, we could potentially treat a number of cancers for which few, if any, treatment options exist."

About CX-2009 and the PROCLAIM-CX-2009 Trial
CX-2009, a PDC that targets cell surface protein CD-166, is being developed for the treatment of solid tumors. CD-166 is highly and homogeneously expressed on multiple tumor types, such as breast cancer, endometrial cancer and prostate cancer. CytomX has demonstrated that CD-166 effectively internalizes antibody-drug conjugates resulting in potent cell killing in-vitro. CX-2009 is designed to target CD-166 specifically in the tumor microenvironment and deliver the tubulin-destabilizing maytansine payload, DM4, to cancer cells. In 2014, CytomX entered into a license agreement with ImmunoGen, Inc. to develop PDCs against a defined number of targets, bringing together CytomX’s proprietary antibody masking technology and tumor-selective protease substrates with ImmunoGen’s highly potent antibody drug conjugate cell-killing agents and engineered linkers. CX-2009 is wholly owned by CytomX.

CX-2009 is being studied within PROCLAIM, CytomX’s international modular umbrella clinical trial program that encompasses the Phase 1/2 development of multiple Probody therapeutics. PROCLAIM-CX-2009 is a dose-finding Phase 1/2 study evaluating CX-2009 as monotherapy in patients with select cancer types, including non-small cell lung cancer, breast cancer, ovarian cancer, endometrial cancer, cholangiocarcinoma (bile duct cancer), head and neck cancer and castration-resistant prostate cancer. The objectives of the study are to establish the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of CX-2009.

More information about the trial is available at ClinicalTrials.gov.

Aduro Biotech Announces First Patient Dosed in Phase 2 Clinical Trial of CRS-207 in Combination with KEYTRUDA® (pembrolizumab) for the Treatment of Patients with Previously Treated Malignant Pleural Mesothelioma

On June 28, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that the first patient has been dosed in the company’s Phase 2 clinical trial in malignant pleural mesothelioma (MPM) (Press release, Aduro Biotech, JUN 28, 2017, View Source [SID1234519704]). The trial, which will involve approximately 35 patients, will evaluate the tolerability, safety and efficacy of CRS-207, Aduro’s LADD (live, attenuated double-deleted) based immunotherapy, in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck (known as MSD outside the United States and Canada), for the treatment of patients with MPM whose disease progressed following prior treatment.

"We are excited to initiate this Phase 2 trial to evaluate the combination of CRS-207 and pembrolizumab, an anti-PD-1 therapy, which we believe has the potential to be a synergistic combination therapy for patients with malignant pleural mesothelioma," said Natalie Sacks, M.D., chief medical officer at Aduro. "Mesothelioma is an aggressive cancer with a poor prognosis and limited treatment options; currently, there are no FDA-approved therapies indicated for second- or third-line treatment. We have received Orphan Drug Designation in the U.S. and E.U. for CRS-207 for this indication, and we are committed to doing all that we can to bring new treatment options to patients facing this difficult disease."

The multicenter, single-arm, open-label Phase 2 study is designed to evaluate the safety and efficacy of CRS-207 with pembrolizumab in adults with previously treated MPM. The trial will be conducted at up to 10 sites and will enroll approximately 35 patients who have failed one to two prior treatments. The primary efficacy endpoint is objective response rate, defined as the proportion of patients with either complete or partial responses. For additional information about the study, please visit www.clinicaltrials.gov (NCT03175172).

Earlier this year, Aduro announced a clinical collaboration with Merck, through a subsidiary, relating to the investigation of CRS-207 used in combination with pembrolizumab for the treatment of MPM. This is the second clinical collaboration formed this year between the two companies, with the first announced in January 2017 relating to the investigation of CRS-207 used in combination with pembrolizumab for the treatment of gastric cancer.

Previously Reported Clinical Data with CRS-207 in Malignant Pleural Mesothelioma
In June 2016, data from a Phase 1b study evaluating CRS-207 alone and in combination with standard chemotherapy in patients with newly-diagnosed MPM were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper). Data from this study demonstrated that CRS-207 induced encouraging anti-tumor responses. Following treatment with the combination of CRS-207 and standard chemotherapy, disease control was observed in 94 percent of the 36 patients evaluated, including 3 percent with a complete response, 56 percent with partial responses, and 36 percent experiencing stable disease. Prior to receiving chemotherapy, patients received two doses of CRS-207 alone. During this period, 31 percent of patients experienced some tumor shrinkage, supporting the clinical activity of single-agent CRS-207. Additionally, paired pre- and on-treatment tumor biopsies demonstrated CRS-207 induced important changes in the tumor microenvironment, including an increase in infiltrating CD8+ T cells and other immune cell types that are thought to be essential for immunotherapy, including dendritic cells and natural killer cells.

About Malignant Pleural Mesothelioma
Mesothelioma is a form of cancer that affects the smooth layer of mesothelial cells that surround the chest, lungs, heart and abdomen. Malignant pleural mesothelioma (MPM), which affects the thin balloon-shaped lining of the lungs, is the most common form of this disease and accounts for approximately 3,000 cases a year in the United States. MPM is an aggressive disease with a poor prognosis. Most MPM patients are not candidates for surgical resection. The tumor-associated antigen mesothelin is overexpressed on the majority of mesothelioma tumors. Currently, there is no U.S. Food and Drug Administration-approved therapy for second- or third-line treatment of MPM.

About LADD and CRS-207
LADD is Aduro’s proprietary platform of live, attenuated double-deleted Listeria monocytogenes strains that have been engineered to generate an innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. CRS-207, the company’s lead LADD product candidate, has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian, endometrial and gastric cancers.

Affimed Presents Preclinical Data on AFM24 and AFM26 at EACR-AACR-SIC 2017

On June 27, 2017 Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, reported the presentation of preclinical data for the Company’s AFM24 and AFM26 programs at the EACR-AACR-SIC 2017 Special Conference in Florence, Italy (Press release, Affimed, JUN 27, 2017, View Source [SID1234519711]).

"With our NK-cell engagers AFM24 and AFM26 we are pursuing two preclinical programs which we believe are ideally suited to exploit NK-cell mediated cytotoxicity to fight cancer," said Dr. Martin Treder, Chief Scientific Officer of Affimed. "Our data for both programs show a well-differentiated profile from competitor products, addressing the need for higher efficacy and better safety."

AFM24 and AFM26 are two first-in-class tetravalent, bispecific NK-cell engagers targeting CD16A, a dominant activating receptor on NK-cells. In addition, AFM24 targets EGFR, while AFM26 binds to BCMA. Corroborating the Company’s earlier data, the studies presented at EACR-AACR-SIC 2017 provided further evidence of favorable safety profiles for both NK-cell engagers and also confirmed their ability to potently and effectively lyse tumor cells, even those with very low target expression. Furthermore, the high affinity to CD16A on NK-cells, resulting in long cell retention binding to NK-cells, and the minimal influence of serum IgG on tumor cell lysis are important differentiating factors of Affimed’s NK-cell platform compared to IgG-based monoclonal antibodies (mAbs).

In detail, AFM24 was shown to be distinguished from cetuximab in vitro and in vivo through higher potency at both high and low EGFR expression levels and in RAS mutant cells, while offering a more favorable safety profile. Single and repeat dose toxicology studies in cynomolgus monkeys demonstrated that AFM24 was well-tolerated at high doses. Further differentiating AFM24 from other therapies, no evidence of skin toxicity, a side effect commonly seen for other anti-EGFR antibodies and for tyrosine kinase inhibitors, was observed.

In addition, the Company presented further data highlighting the preclinical progress of AFM26. The NK-cell engager was able to elicit efficient tumor cell lysis in both cell lines and primary cells, even at very low BCMA expression levels. In addition, the amount of inflammatory cytokines released in vitro by cells treated with AFM26 was markedly lower than those of cells treated with a BCMA/CD3 T-cell engager. Furthermore, in contrast to approved mAb therapies such as daratumumab and elotuzumab, AFM26 did not induce NK-cell depletion in vitro.

Taken together, the results presented at EACR-AACR-SIC 2017 support the therapeutic rationale of redirecting NK-cells to tumors through bispecific tetravalent NK-cell engagers, which offers a novel mode of action addressing limitations of other therapies.