On April 16, 2018 Bristol-Myers Squibb Company (NYSE: BMY) reported two-year overall survival (OS) data from CheckMate -141, a Phase 3 open-label, randomized trial evaluating Opdivo (nivolumab) compared with investigator’s choice chemotherapy (cetuximab, docetaxel or methotrexate) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) after failure on platinum-based therapy (Press release, Bristol-Myers Squibb, APR 16, 2018, View Source [SID1234525334]). Patients treated with Opdivo experienced a 32% reduction in the risk of death after a minimum two years of follow-up (HR 0.68; 95% CI: 0.54 to 0.86), with a median OS of 7.7 months (95% CI: 5.7 to 8.8) compared with 5.1 months (95% CI: 4.0 to 6.2) for standard chemotherapy. The two-year survival rate for Opdivo was 16.9% (95% CI: 12.4 to 22.0) versus 6.0% (95% CI: 2.7 to 11.3) for standard chemotherapy. The safety profile for Opdivo at two-year follow-up was consistent with previous analyses from the study.

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These data will be presented today as an oral presentation (Abstract #CT116) at 4:35 PM CDT, N Hall C (Level 1) during the Updates in Immuno-Oncology Trials session at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago.

"The introduction of Immuno-Oncology has the potential to change the treatment landscape of squamous cell carcinoma of the head and neck, compared with the standard of care," said Robert L. Ferris, M.D., Ph.D., a cancer immunotherapist and Director, UPMC Hillman Cancer Center, Pittsburgh, PA. "The sustained overall survival benefit demonstrated by nivolumab in this study is encouraging in SCCHN, which historically has a median survival of less than six months."

The sustained Opdivo OS benefit was observed across PD-L1 expressors and non-expressors in patients with recurrent or metastatic SCCHN. At the two-year follow-up in patients treated with Opdivo whose tumors had PD-L1 expression ≥ 1%, risk of death was reduced by 45% (HR 0.55; 95% CI: 0.39 to 0.78). For patients treated with Opdivo whose tumors had PD-L1 expression <1%, risk of death at two years was reduced by 27% (HR 0.73; 95% CI: 0.49 to 1.09) versus standard chemotherapy.

"Opdivo is the only I-O treatment for squamous cell carcinoma of the head and neck to have shown a significant overall survival benefit versus chemotherapy at the primary analysis. These two-year follow-up data show a sustained long-term overall survival benefit for patients, across PD-L1 expression levels and regardless of HPV status," said Shinta Cheng, M.D., Ph.D., development lead, Bristol-Myers Squibb. "These data showing the durability of this benefit reinforce our ongoing commitment to continuing research with the hope of delivering what matters most to patients fighting cancer: long-term survival."

There were no statistically significant differences between the two arms for PFS (HR 0.87; 95% CI: 0.68 to 1.11) for Opdivo and investigator’s choice, respectively. The safety profile of Opdivo with a two-year follow-up was consistent with previous analyses and with prior studies of Opdivo in patients with melanoma and non-small cell lung cancer. Grade 3-4 treatment-related adverse reactions occurred in 15.3% of patients receiving Opdivo versus 36.9% of patients receiving investigator’s choice.

About CheckMate -141 (Abstract #CT116)
CheckMate -141 is a global phase 3, open-label, randomized trial evaluating Opdivo versus investigator’s choice chemotherapy in patients with recurrent or metastatic SCCHN who had tumor progression during or within six months of receiving platinum-based therapy administered in the adjuvant, neo-adjuvant, primary (unresectable locally advanced) or metastatic setting. Patients were included regardless of their HPV or PD-L1 status. Patients were randomized 2:1 to receive Opdivo 3 mg/kg intravenously over 60 minutes every two weeks (n=240), or investigator’s choice (n=121) of methotrexate 40 to 60 mg/m2 intravenously weekly, docetaxel 30 to 40 mg/m2 intravenously weekly, or cetuximab 400 mg/m2 intravenously once then 250 mg/m2 weekly. The primary endpoint is OS. The trial’s secondary endpoints include progression-free survival (PFS) and objective response rate (ORR).

About Head & Neck Cancer
Cancers that are known as head and neck cancers usually begin in the squamous cells that line the moist mucosal surfaces inside the head and neck, such as inside the mouth, the nose and the throat. Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease. Squamous cell carcinoma of the head and neck (SCCHN) accounts for approximately 90% of all head and neck cancers, with global incidence expected to increase by 17% between 2012 and 2022. Risk factors for SCCHN include tobacco and alcohol consumption. The human papillomavirus (HPV) infection is also a risk factor leading to rapid increase in oropharyngeal SCCHN in Europe and North America. Quality of life is often impacted for SCCHN patients, as physiological function (breathing, swallowing, eating, drinking), personal characteristics (appearance, speaking, voice), sensory function (smell and hearing), and psychological/social function can be affected.

On April 16, 2018 Leap Therapeutics, Inc. (NASDAQ:LPTX) reported that presented nonclinical and clinical data on DKN-01, Leap’s anti-DKK1 monoclonal antibody, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2018 Annual Meeting (Press release, Leap Therapeutics, APR 16, 2018, View Source;p=RssLanding&cat=news&id=2342693 [SID1234525349]). The presentation highlighted the immunomodulatory activity of DKN-01 in nonclinical experiments and preliminary results from the dose escalation phase of the clinical study evaluating DKN-01 in combination with the Merck (known as MSD outside the United States and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced esophagogastric cancer.

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Nonclinical Data:
Nonclinical studies demonstrated the activity of DKK1 inhibition in enhancing innate immunity and the potential for combination with immune checkpoint inhibitors. mDKN-01, the murine form of DKN-01, reduced myeloid-derived suppressor cells (MDSCs), increased PD-L1 levels on MDSCs, and enhanced expression of T-cell chemoattractants. These innate mechanisms, promoting an inflammatory tumor microenvironment, are complementary to immune checkpoint inhibition. In a syngeneic tumor model, mDKN-01 had additive activity with anti-PD-1 therapy as compared to either antibody administered alone.

Clinical Data:
Preliminary results from the dose escalation phase of the clinical study evaluating the combination of DKN-01 and KEYTRUDA in patients with advanced esophagogastric cancer demonstrated that the combination was well tolerated with early signals of clinical activity:
Four out of five patients enrolled at the highest tested dose of DKN-01 were naïve to anti-PD-1/PD-L1 therapy and evaluable for response. One patient had a partial response with a 66% reduction in target tumor volume. This patient had progressed on two prior systemic therapies and had a tumor that was known to be KRAS amplified, microsatellite stable (MSS), and PD-L1 negative; a phenotype typically less responsive to anti-PD-1 therapy. Three patients had stable disease, two of whom remain on study through at least four cycles.

Two patients enrolled in the escalation phase were refractory to anti-PD-1/PD-L1 therapy and currently have had a best response of stable disease. One of these patients also had a tumor that was KRAS amplified, MSS, and PD-L1 negative and has been on study for six cycles with an initial 10% reduction in tumor burden.
The DKN-01 and KEYTRUDA expansion combination continues to enroll patients who are naïve to anti-PD-1/PD-L1 therapy (n=40) and patients who are refractory to anti-PD-1/PD-L1 therapy (n=15).

On April 16, 2018 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported that the Company’s randomized, Phase 2b METRIC Study of glembatumumab vedotin compared to Xeloda (capecitabine) in patients with metastatic triple-negative breast cancers that overexpress gpNMB failed to meet its primary endpoint, progression-free survival (PFS) as assessed by an independent, central reading of patient scans (Hazard ratio = 0.95; median PFS: glembatumumab vedotin 2.9 months vs. Xeloda 2.8 months; p=0.76) (Press release, Celldex Therapeutics,APR 16, 2018, View Source [SID1234525681]). There was no significant advantage for glembatumumab vedotin in key secondary endpoints, including overall response rate, duration of response and overall survival. The glembatumumab vedotin safety profile was consistent with prior experience.

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"Triple-negative breast cancer is a very difficult disease to treat, and we are extremely disappointed for patients that the METRIC Study was not successful," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "On behalf of Celldex, I want to express our gratitude to the METRIC investigators, patients and families who participated in this study. Based on these results, we have also made the decision to discontinue the glembatumumab vedotin program across all indications and are currently prioritizing our pipeline, which includes five candidates in ongoing clinical studies. In line with this, we are evaluating our operational and workforce needs to extend our financial resources and direct them to continued pipeline advancement. Once we solidify these plans, we intend to update investors."

Celldex’s clinical-stage pipeline includes the following compounds:

Varlilumab, a CD27 agonist, currently completing a Phase 2 study in combination with Opdivo in multiple indications with data expected to be presented at multiple medical meetings in 2018;
CDX-3379, an ErbB3 inhibitor, which is expected to complete enrollment in the first stage of a Phase 2 study in combination with Erbitux in head and neck cancer during the third quarter of 2018;
CDX-014, a TIM-1 targeted agent, which is actively enrolling patients in a Phase 1 study in renal cell and ovarian clear cell carcinomas;
CDX-1140, a CD40 agonist, which is actively enrolling patients in a Phase 1 study in various solid tumors; and,
CDX-301, a dendritic cell mobilizer, currently being studied in an investigator-sponsored study in combination with radiation therapy in advanced non-small cell lung cancer. Data from this study were presented in a plenary session at the AACR (Free AACR Whitepaper) Annual Meeting on Sunday, April 15, 2018.
Celldex believes its pipeline prioritization and organizational restructuring efforts will extend financial resources beyond the guidance issued in the Company’s year-end 2017 earnings press release and associated filings. The Company plans to provide revised guidance in its first quarter 2018 financial results in early May.

Webcast and Conference Call
Celldex executives will host a conference call at 8:00 a.m. ET today to discuss topline METRIC results. The conference call will be webcast live over the internet and can be accessed by going to the "Events & Presentations" page under the "Investors & Media" section of the Celldex Therapeutics website at www.celldex.com. The call can also be accessed by dialing (866) 743-9666 (within the United States) or (760) 298-5103 (outside the United States). The passcode is 7786951.

A replay of the call will be available approximately two hours after the live call concludes through April 23, 2018. To access the replay, dial (855) 859-2056 (within the United States) or (404) 537-3406 (outside the United States). The passcode is 7786951. The webcast will also be archived on the Company’s website.

About METRIC
The METRIC study is a randomized Phase 2b study of glembatumumab vedotin in patients with metastatic triple-negative breast cancers that overexpress gpNMB. In this indication, overexpression is defined as greater than or equal to 25% of tumor cells testing positive for gpNMB. Patients were randomized 2 to 1 to either glembatumumab vedotin or to capecitabine, also known by the tradename Xeloda, as a comparator. In total, 327 patients were enrolled into METRIC. The primary endpoint of the study is progression-free survival (PFS), which is defined as the time from randomization to the earlier of disease progression, assessed based on an independent, central reading of patient scans, or death due to any cause. The study called for 203 progression events for evaluation of the primary endpoint. The sum of the data, including the secondary endpoints of response rate, overall survival, duration of response and safety, are also important in assessing clinical benefit.

About Glembatumumab Vedotin
Glembatumumab vedotin is a fully human monoclonal antibody-drug conjugate (ADC) that targets glycoprotein NMB (gpNMB). gpNMB is a protein overexpressed by multiple tumor types, including breast cancer, melanoma, lung cancer, uveal melanoma and osteosarcoma. The gpNMB-targeting antibody, CR011, is linked to a potent cytotoxic, monomethyl auristatin E (MMAE), using Seattle Genetics’ proprietary technology. Glembatumumab vedotin is designed to be stable in the bloodstream but to release MMAE upon internalization into gpNMB-expressing tumor cells, resulting in a targeted cell-killing effect.

Xeloda is a registered trademark of Genentech, Inc. Opdivo is a registered trademark of Bristol-Myers Squibb. Erbitux is a registered trademark of Eli Lilly & Co.

On April 16, 2018 Oncoceutics, Inc. reported that the first patient has been treated in a Phase I/II clinical trial of ONC201 in combination with ixazomib and dexamethasone in relapsed and/or refractory multiple myeloma (Press release, Oncoceutics, APR 16, 2018, View Source [SID1234558369]). The trial, led by Ajai Chari, MD, Associate Professor at the Icahn School of Medicine at Mount Sinai, is entitled "A Phase I/II Study of the Addition of Ixazomib to ONC201 and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma" (NCT03492138) and seeks to combine two oral medications that have shown synergy against multiple myeloma in preclinical models. The study will enroll up to 36 adult patients and will evaluate the safety and tolerability of ONC201 in combination with ixazomib and dexamethasone in Phase I and determine the two-month disease control rate as the primary endpoint of Phase II.

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While Oncoceutics is currently focused on clinical trials of ONC201 in high-grade gliomas as its lead indication, the company continues to advance a number of clinical programs in B cell malignancies because they have shown some of the highest sensitivity against ONC201 in pre-clinical models. Oncoceutics currently has two programs in multiple myeloma: "Oral ONC201 in Relapsed/Refractory Multiple Myeloma" (NCT02863991) and the combination trial with ixazomib described above.

Multiple myeloma is highly sensitive to proteasome inhibitors that activate the integrated stress response, the same pathway activated by ONC201 treatment through unique triggers. ONC201 synergizes with proteasome inhibitors since they converge on some of the same downstream effects as ONC201 even though they use distinct triggers in tumor cells. Based on this rationale, which is supported by published preclinical studies (Prabhu et al, Cell Cycle 2018; Tu et al, Neoplasia 2017), this clinical trial will test the combination of ONC201 with ixazomib and dexamethasone. Ixazomib, which goes by brand name NINLARO, is an oral proteasome inhibitor developed by Takeda Pharmaceutical Company. It is FDA approved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In addition to the U.S., NINLARO is approved in more than 50 countries.

"We are excited to have the opportunity to test these two oral agents that have demonstrated efficacy against multiple myeloma in pre-clinical settings to provide therapies to patients with refractory/relapsed multiple myeloma that are in need of novel therapies," said Ajai Chari, Associate Professor, Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mt. Sinai.

On April 16, 2018 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing investigational drugs for the treatment of orphan oncology indications, reported that business update and announced 2017 financial results.

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Business Update
Earlier today, Mateon announced the raise of additional capital in a private placement transaction with accredited investors. In addition to general corporate purposes, the additional capital will be prioritized towards the advancement of the company’s two drug development programs:
Using OXi4503 as a treatment for relapsed refractory acute myeloid leukemia
Using CA4P as an immuno-oncology agent as a treatment for advanced melanoma
Both of the company’s clinical development programs have potential to generate additional new clinical data before the end of 2018, with new data from OXi4503 in acute myeloid leukemia (AML) expected before initial data from CA4P as an immuno-oncology agent. The company plans to continue to pursue corporate collaboration opportunities with larger pharmaceutical companies for both of these programs.

The following provides an overview of the company’s two drug development programs:
OXi4503 as a treatment for AML

Mateon has an on-going clinical trial in which its investigational drug OXi4503 is being tested as a new treatment for relapsed/refractory AML and myelodysplastic syndromes (MDS). In this clinical trial, we have completed five ascending dose cohorts using OXi4503 in combination with cytarabine, but subsequently paused enrollment due to lack of sufficient funds. Following the financing announced earlier today, the trial is again opening for patient enrollment. Newly enrolled patients will enter into the trial’s sixth cohort (12.2 mg/m2 of OXi4503; a 25% greater dose than the most recently completed 5th cohort). In the completed fifth cohort, we observed two complete remissions (50%) after one cycle of treatment with 9.76 mg/m2 of OXi4503, and did not observe any dose-limiting toxicities. Among the first four cohorts (lower doses of OXi4503 ranging from 3.75 to 7.81 mg/m2), we observed three complete remissions (18%), each occurring after two cycles of treatment. Because of these promising data, we are planning to enroll a higher number of patients into the sixth cohort in order to better evaluate the potential efficacy of OXi4503. Initial data from the sixth cohort is expected this summer.

CA4P as an Immuno-Oncology Agent
CA4P in combination with immuno-oncology agents is a promising investigational new treatment regimen for patients with advanced cancer who have failed standard therapies. This combination regimen, when studied in animal models of different cancer types, has been shown to increase tumor associated immune responses, tumor regressions, and overall survival compared to immuno-oncology agents alone. While there exist a number of new FDA-approved immuno-oncology agents which have significantly improved treatment options for patients with advanced cancer, unfortunately relatively few of these patients achieve a durable clinical response after treatment with these agents alone. New drugs which enhance the efficacy of these drugs, such as CA4P has been shown to do in animals, are greatly needed.

The mechanism-of-action of CA4P appears to be both unique and promising. CA4P causes rapid and widespread ischemic necrosis of the tumor shortly after infusion. This potent and tumor-specific type of necrosis in turn causes a potent and tumor-specific immune response. Animal models, for example, show that CA4P in combination with an immuno-oncology agent significantly enhances the number and activity of cancer-fighting T-cells within tumors compared to the immuno-oncology agent alone. In these animal models, these cancer-fighting T-cells were shown to be evident throughout the tumor and were associated with twice the amount of tumor necrosis than observed in treatment with the immuno-oncology agent alone. Accordingly, we believe CA4P may result in more and/or better clinical responses in patients with certain advanced cancers, including in patients who either have not experienced a response to immuno-oncology therapy, or in patients who have initially responded but subsequently progressed after treatment.

The next step for establishing CA4P as a safe and effective immuno-oncology agent is to initiate a clinical trial in a setting where immuno-oncology agents are currently used as standard therapy but have historically been associated with a low overall durable response rate. Therefore, Mateon plans to initiate a clinical trial evaluating CA4P in combination with an approved immuno-oncology agent, Opdivo (nivolumab, marketed by Bristol-Myers Squibb), in patients with advanced metastatic melanoma who have previously failed Opdivo and consequently have a poor prognosis. Our goal is to improve the clinical outcomes for these patients, and obtain initial data from the study before the end of the year.

"We are excited about testing the ability of CA4P to enhance the efficacy of Opdivo in advanced melanoma in a new clinical trial," said William D. Schwieterman, M.D., Chief Executive Officer of Mateon Therapeutics. "Because CA4P works rapidly, specifically and powerfully in many tumor types to induce tumor-specific ischemic necrosis, it could be an ideal agent for boosting tumor-specific immune responses and enhancing the efficacy of currently approved immuno-oncology agents.
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Financial Results
For the year ended December 31, 2017, Mateon reported a net loss of $13.8 million, an increase of $0.1 million from the net loss of $13.7 million for the year ended December 31, 2016. R&D expenses increased to $10.5 million in 2017 compared to $8.8 million in 2016, while general and administrative expenses decreased to $3.4 million in 2017 compared to $5.0 million in 2016.
At December 31, 2017, Mateon had cash and cash equivalents of $1.1 million.