On June 3, 2019 Oncopeptides AB (Nasdaq Stockholm: ONCO), a pharmaceutical company focused on the development of targeted therapies for difficult-to-treat hematological cancers, reported new data presented at the the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from its Phase 1/2 O-12-M1 clinical study of lead candidate melflufen (Press release, Oncopeptides, JUN 3, 2019, View Source [SID1234536810]). The data demonstrate that melflufen may offer positive disease stabilization and favorable time to next treatment (TTNT) outcomes in heavily-pretreated patients with relapsed/refractory multiple myeloma (RRMM).

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Overall conclusions from the data presented include:

Melflufen plus dexamethasone treatment results in disease stabilization in 76% of RRMM patients, which translates to a median TTNT of 7.9 months (10.6 months when censoring at time of death), which compares favorably with other relevant trials.
A median OS of 20.7 months in an advanced RRMM population, suggesting that melflufen therapy is associated with a long?term benefit and allows patients to receive further treatment to control disease.
Results support those of previous data showing the promising efficacy profile of melflufen for the treatment of RRMM.
The data is presented by Professor Paul G. Richardson, MD, RJ Corman Professor of Medicine at Harvard Medical School and Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, USA.

Oncopeptides recently announced that, following discussions with the U.S. Food & Drug Administration (FDA), the company has initiated the preparation for submitting a New Drug Application (NDA) for accelerated approval of melflufen for the treatment of patients with triple-class refractory multiple myeloma. The company targets to submit the application in the first quarter of 2020 based on the positive data from the ongoing Phase 2 HORIZON clinical trial.

"We are committed in helping patients with myeloma get access to melflufen given the safety and efficacy profile that is emerging from our clinical trials," said Jakob Lindberg, CEO of Oncopeptides. "In addition to the data presented at ASCO (Free ASCO Whitepaper), data from the melflufen clinical programs have also been selected for four presentations at the 2019 EHA (Free EHA Whitepaper) Annual Congress, including updated data from the HORIZON Phase 2 pivotal clinical trial that will serve as the foundation for our NDA submission."

The full poster presented at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting can be found on the company webpage under:

www.oncopeptides.com / Investors & Media / Presentations / 2019 ASCO (Free ASCO Whitepaper) Annual Meeting – poster

About the O-12-M1 Clinical Trial
O?12?M1 is a Phase 1/2 study with melflufen plus dexamethasone in 62 patients with RRMM who had ≥2 prior lines of therapy, prior exposure to at least an IMiD and a proteasome inhibitor, and disease progression on last line of therapy. Final study results were presented at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Summary of O-12-M1 Data
At the time of data cutoff on November 9, 2017, 45 patients had been treated with 40 mg melflufen and dexamethosone. Median age was 66 years (47-78). 60% of patients were ISS stage II/III and 44% were high-risk cytogenetics. Patients had four median prior lines of therapy, with 91% of patients being single refractory, 67% of patients double refractory and 7% triple refractory. Further, 53% of patients were alkylator refractory. At data cutoff, 44 pts (98%) discontinued melflufen + dexamethasone, mainly due to adverse events (40%) and PD (31%). 27 patients received subsequent therapy. Median time from start of melflufen and dexamethasone to first subsequent therapy or death (TTNT), whichever occurred first, was 7.9 months (95% CI: 5.68-11.01). The majority of patients’ (52%) next therapy was single-agent with or without steroid therapy, and approximately half of patients receiving subsequent therapy (44%) received at least two subsequent lines of therapy.

Table: TTNT with Melflufen in O-12-M1 and Other Agents in RRMM

TTNT with Melflufen in O-12-M1

For further information, please contact:
Jakob Lindberg, CEO of Oncopeptides
E-mail: [email protected]
Telephone: +46 (0)8 615 20 40

Rein Piir, Head of Investor Relations at Oncopeptides
E-mail: [email protected]
Cell phone: +46 (0)70 853 72 92

This information was submitted for publication at 15.00 CET, June 3, 2019

About melflufen
Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. It belongs to the novel class Peptidase Enhanced Cytotoxics (PEnC), which is a family of lipophilic peptides that exhibit increased activity via peptidase cleavage and have the potential to treat many cancers. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the peptidase cleavage, and induces irreversible DNA damage and apoptosis. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.

On June 3, 2019 Novartis reported new data and clinical trial updates in NSCLC at the ASCO (Free ASCO Whitepaper) 2019 Annual Meeting. This includes primary efficacy results from the GEOMETRY mono-1 Phase II clinical trial demonstrating that investigational MET inhibitor capmatinib (INC280) shows promise as a potential treatment option for patients with locally advanced or metastatic NSCLC that harbor MET exon-14 skipping mutation (Press release, Novartis, JUN 3, 2019, View Source [SID1234536809]). There are currently no approved targeted therapies to treat this particularly aggressive form of NSCLC. Results of the Phase II study will be presented at an oral session today at ASCO (Free ASCO Whitepaper), June 3, 2019, at 8:00 a.m. CDT (Abstract #9004)[1].

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GEOMETRY mono-1 is an international, prospective, multi-cohort, non-randomized, open-label study evaluating 97 adult patients with locally advanced or metastatic NSCLC harboring MET exon-14 skipping mutation who received capmatinib tablets 400 mg orally twice daily. Primary efficacy results among treatment-naive patients (Cohort 5b: 28 patients) were a 68% overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1 (95% CI: (47.6 – 84.1)). Forty-one percent of previously treated NSCLC patients (Cohort 4: 69 patients) also responded (95% CI: (28.9 – 53.1)). Data on median duration of response (DOR), a key secondary endpoint, was 11.14 months (95% CI: (5.55 – NE)) and 9.72 months (95% CI: (5.55 – 12.98)), respectively. Intracranial activity in 54% (n=7/13) of patients, including some cases of complete resolution of brain lesions, was also observed by ad hoc neuro-radiologist review in patients with brain lesions. All results were based on independent assessment by the BIRC, and all tumor CT scans were evaluated in parallel by two radiologists to confirm the response.

The most common treatment related adverse events (AE) (>=10% all grades) across all cohorts (n=334), were peripheral edema (42%), nausea (33%), creatinine increase (20%), vomiting (19%), fatigue (14%), decreased appetite (13%) and diarrhea (11%); the majority of the AEs were grades 1/2.

"New lung cancer treatment options are critical, as this deadly disease affects more than 2 million new patients around the world each year," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "The GEOMETRY mono-1 results are encouraging, and we look forward to discussing these results with health authorities with the hope of bringing this targeted treatment option to people with this aggressive type of lung cancer."

Capmatinib Granted Orphan Drug and Breakthrough Therapy Designation Status
The U.S. Food and Drug Administration recently granted capmatinib Breakthrough Therapy Designation for patients with metastatic NSCLC harboring MET exon-14 skipping mutation with disease progression on or after platinum-based chemotherapy. Previously, both the U.S. FDA and Japan’s Pharmaceuticals and Medical Devices Agency recognized capmatinib with Orphan Drug status. It is estimated that 3% to 4% of all patients with NSCLC have an identified MET mutation[3].

"The efficacy observed with capmatinib in the GEOMETRY mono-1 trial is promising," said Juergen Wolf, MD, University Hospital, Cologne. "In addition to positive overall response rate among first-line patients with the MET mutation, the duration for the responses, including the activity in the brain, and capmatinib’s safety profile are important milestones for this patient population. As a group, patients with MET mutated NSCLC often require special clinical considerations, as they are generally older and with poor prognosis further limiting their treatment options."

About GEOMETRY mono-1
GEOMETRY mono-1 is an international, prospective, multi-cohort, non-randomized, open-label Phase II study to evaluate the efficacy and safety of single-agent capmatinib (INC280) in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with locally advanced or metastatic NSCLC harboring MET exon-14 skipping mutation (centrally confirmed) were assigned to Cohorts 4 (previously treated patients) or 5B (treatment-naive), regardless of MET amplification/gene copy number, and received 400 mg capmatinib tablets orally twice daily. The primary endpoint was ORR based on the BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by the BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=28) of 67.9% (95% CI: 47.6 – 84.1) and an ORR of 40.6% (95% CI: 28.9 – 53.1) in the previously treated patients (n=69). Median DOR was 11.14 months (95% CI: 5.55-NE) in treatment-naive patients and 9.72 months (95% CI: 5.55-12.98) in previously treated patients[1].

The most common treatment-related AEs included peripheral edema, nausea, creatinine increase and vomiting. Of patients treated with capmatinib, 84% experienced an AE, with 36% having grade 3/4 AEs (only 4.5% were Grade 4)[1].

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

Studying Tumor-Promoting Inflammation in Lung Cancer – Ongoing CANOPY Trials
Trials in Progress (TiP) updates on the CANOPY clinical program were also included in the ASCO (Free ASCO Whitepaper) updates. CANOPY is made up of three randomized, double-blind and placebo-controlled Phase III trials evaluating canakinumab (ACZ885), a selective IL-1ß inhibitor (Abstract #TPS9124) [4],[5].

CANOPY-A is a Phase III multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of canakinumab as adjuvant therapy in adult subjects with stages II-IIIA and NSCLC following complete surgical resection. The primary endpoint is disease-free survival (Abstract #7013).
CANOPY-1 is a randomized, double-blind, placebo-controlled, Phase III study investigating canakinumab versus placebo in combination with platinum-based chemotherapy (CTx) and pembrolizumab in previously untreated patients with stage IIIB/IIC-IV squamous and non-squamous NSCLC. The study will evaluate the incidence of dose-limiting toxicity (DLT) in the first 42 days of treatment, as well as PFS and overall survival (OS).
CANOPY-2 is a randomized, double-blind, placebo-controlled, Phase III study investigating canakinumab or placebo plus docetaxel in stage IIIB-IV NSCLC patients previously treated with PD-1 or PD-L1 inhibitors, as well as CTx. The primary endpoints are incidence of DLT in the first 42 days of treatment and OS.
Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and more than 2 million new cases of lung cancer are diagnosed each year[2]. Despite treatment advances, patients with NSCLC still have a poor prognosis and limited treatment options. This includes the nearly 70% of NSCLC patients who have a genomic mutation that may be targeted with available therapies[6]. To determine the most appropriate treatment, medical organizations recommend genomic testing for patients with lung cancer[7].

Novartis Oncology’s research has helped transform treatment approaches for patients living with NSCLC. Novartis continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds in NSCLC, including those that target genetic biomarkers and tumor promoting inflammation.

On June 3, 2019 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing potential new therapies for cancer, reported that updated data presented at ASCO (Free ASCO Whitepaper) 2019 from a Phase 1b study of investigational ME-401, a selective oral inhibitor of PI3K delta, demonstrate an 80% overall response rate in patients with relapsed or refractory (r/r) follicular lymphoma (FL) (n= 50). Additionally, the data demonstrate (Press release, MEI Pharma, JUN 3, 2019, View Source [SID1234536808]):

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Comparable overall response rates, ranging from 75% to 83%, across patient groups receiving ME-401 as a monotherapy or in combination with rituximab, and in patient groups dosed with ME-401 once daily on a continuous schedule (CS) or on an intermittent schedule (IS) of once daily for the first 7 days of a 28-day cycle after 2 months of continuous dosing.
A lower rate of delayed, grade 3 adverse events (e.g. 8.7% diarrhea/colitis for IS dosing) observed in patients in the IS group.
Durable responses in both CS and IS groups with no median yet reached.
The ME-401 ASCO (Free ASCO Whitepaper) 2019 poster can be accessed on the MEI Pharma website.

Andrew D. Zelenetz, M.D., Ph.D., Principal Investigator of the Phase 1b study and Professor of Medicine at Weill Cornell Medical College, Medical Director of Quality Informatics at Memorial Sloan Kettering Cancer Center, and Chair of the National Comprehensive Cancer Network’s Non-Hodgkin Lymphoma Guideline Panel, commented: "ME-401 is a second generation PI3K inhibitor specific for the delta isoform that has excellent activity in CLL and FL. This class of drugs has been associated with immune related toxicities which are also seen with ME-401 dosed continuously. However, we explored a novel dosing strategy with intermittent drug exposure (one week on, 3 weeks off) that appears to markedly reduce toxicity and maintain efficacy. If validated, this could expand the role of PI3K in B-cell malignancies. A prospective randomized phase 2 trial is underway comparing intermittent to continuous dosing aiming to confirm these preliminary findings."

"The Phase 1b data remain very encouraging and support the further investigation of ME-401 for patients with relapsed or refractory follicular lymphoma," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "ME-401 further represents a unique opportunity to more broadly leverage the utility of PI3K as a central component of B-cell signaling and potentially offer a treatment option across multiple B-cell malignancies either as a monotherapy or in combination with other therapies."

MEI has initiated a global Phase 2 study to evaluate the efficacy, safety, and tolerability of ME-401 as a single agent in patients with follicular lymphoma after failure of at least two prior systemic therapies including chemotherapy and an anti-CD20 antibody. The Phase 2 study, now labeled the TIDAL study ‘(Trials of PI3K DeltA in Non-Hodgkin’s Lymphoma), is intended to support an accelerated approval marketing application with the U.S. Food and Drug Administration.

ME-401 Phase 1b Clinical Study
The ongoing Phase 1b clinical study is evaluating ME-401 as a monotherapy and in combination with rituximab or with zanubrutinib in patients with r/r B-cell malignancies. Over 85 patients have been enrolled to date, including 54 patients with r/r FL reported on in the ASCO (Free ASCO Whitepaper) 2019 poster. Sixty-five percent (35/54) of r/r FL patients had 2 or more prior lines of therapy. Of the 50 evaluable r/r FL patients, 52% (26/50) were a group of FL patients with progression of disease within 24 months (POD24) of initial immunochemotherapy, which typically have a poor prognosis compared to other r/r FL patients.

ME-401 was administered once daily at 60 mg for 2 28-day cycles and then on an intermittent schedule of once daily dosing for the first 7 days of each subsequent 28-day cycle (i.e. the intermittent schedule or IS). A previous cohort of monotherapy patients in the study was treated with ME-401 administered continuously once daily or were switched to the intermittent schedule in later cycles.

The overall response rate in patients with r/r FL was 80% (40/50), with 20% (10/50) achieving a complete response. Patients receiving monotherapy achieved a 79% (30/38) overall response rate and patients receiving ME-401 in combination with rituximab achieved an 83% (10/12) overall response rate. The group of patients receiving IS dosing achieved a 75% (15/20) overall response rate and patients receiving the CS dosing achieved an 83% (25/30) overall response rate. The response rate among POD24 patients was 92% (24/26).

Evaluable R/R FL Patients

Overall Response

All groups (N = 50)

CR

40 (80%)

10 (20%)

By treatment arm

ME-401 monotherapy (N = 38)

ME-401 + rituximab (N = 12)

30 (79%)

10 (83%)

By schedule

IS Group (N = 20)

CS Group (N = 30)

15 (75%)

25 (83%)

The majority of responses, 88% (35/40), had an objective response by the first two treatment cycles and the achieved responses, to date, are durable; neither median duration of response nor median progression-free survival has been reached. Median follow-up for duration of response in the IS group is 8.8 months (range: 1.9-15.5) and 8.3 months in the CS group (range: 3.0-25.8). Median follow-up for progression free survival is 5.5 months in the IS group (range: 0.9-15.5) and 6.5 months in the CS group (range: 0.9-25.8). Four patients in the IS group and 2 patients in the CS group that were switched to IS dosing experienced progressive disease and reverted to CS dosing to continue treatment.

ME-401 was generally well-tolerated and no grade 4 or grade 5 adverse events have been observed in the Phase 1b study. Among drug related grade 3 adverse events of special interest, the most common are diarrhea/colitis at 8.7% (2/23) on IS dosing and 16.1% (5/31) on CS dosing, and rash with none on IS dosing and 12.9% (4/31) on CS dosing. Four patients, each on the continuous schedule, discontinued due to an adverse event.

The rate of the development of delayed, grade 3 adverse events was improved in patients on the intermittent dosing schedule. There were no isolated grade 3 elevations in ALT and AST; such elevations were transient and in each case were associated with grade 3 diarrhea or rash.

Adverse Events of
Special Interest

Grade 3

CS Group

(N = 31)

IS Group

(N = 23)

Diarrhea/colitis

5 (16.1%)

2 (8.7%)

Rash, all types

4 (12.9%)

0

ALT increased

2 (6.5%)

1 (4.3%)

AST increased

2 (6.5%)

0

Pneumonia

2 (6.5%)

0

Mucositis

1 (1.9%)

0

On June 3, 2019 Dynavax Technologies Corporation (NASDAQ: DVAX), reported increasingly favorable results from the Phase 1b/2 (SYNERGY-001), open-label, multicenter study of the combination of SD-101 and KEYTRUDA (pembrolizumab) in advanced melanoma patients who are naïve to anti-PD-1/PD-L1 treatment (Press release, Dynavax Technologies, JUN 3, 2019, View Source [SID1234536807]). The results were presented today in a poster session at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"To consistently see an overall response rate above 70% among advanced melanoma patients, which has historically been a difficult population to treat, is very encouraging and exciting," said Robert Janssen, M.D., chief medical officer of Dynavax. "Additionally, in response to treatment, we have seen immunologically cold tumors reach similarly high levels of immune cell activation as immunologically hot tumors."

The Phase 1b/2 clinical study (NCT02521870) in patients with advanced melanoma is ongoing. In the study, SD-101 is administered intratumorally with 8 mg in 1 lesion or 2 mg in 1–4 lesions combined with intravenous administration of 200 mg of pembrolizumab.

Key highlights from the clinical data presentation include:

Efficacy:
º The overall response rate (ORR) in the SD-101 2 mg/lesion group (76%) was higher than in the SD-101 8 mg/lesion group (49%)
º The median duration of response (DOR) in both groups has not been reached, with the lower bound of the 95% confidence interval of at least 14 months
º The 18-month progression free survival (PFS) rate in the SD-101 2 mg/lesion group (72%) was higher than in the SD-101 8 mg/lesion group (36%)
º Similar rates of responses occurred in patients with PD-L1 negative tumors and PD-L1 positive tumors
º Tumor shrinkage has been observed in both injected and non-injected lesions, including visceral lesions such as the liver and lung

Immunologically cold tumors are a therapeutic challenge for anti-PD-1 therapy; the ability of SD-101 with pembrolizumab to convert cold tumors (PD-L1 negative, low IFNγ and T cell signature at baseline) into T cell rich tumors is demonstrated by biomarker data in the samples tested
º This ability to convert cold into inflamed tumors is consistent with similar effects in head and neck squamous cell carcinoma (HNSCC) (ASCO 2019, Abstract 6039)

The superior induction of infiltrating effector immune cells in lesions treated with the 2 mg/lesion dose compared with 8 mg/lesion is consistent with the increased response observed

The combination of SD-101 and pembrolizumab was well tolerated, consistent with previous report
º AEs associated with SD-101 were transient, mild to moderate injection-site reactions and flu-like symptoms that were manageable with over-the-counter medications
º No increase in immune-related AEs over pembrolizumab monotherapy were observed
A table accompanying this announcement is available at View Source

The ORR in patients with BRAF mutant tumors who received 2 mg/lesion (n=18) was 61%
The ORR in patients with PD-L1 negative tumors who received 2 mg/lesion (n=14) was 79%
In addition, the company presented data from the Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced/metastatic melanoma resistant to anti-PD-1/PD-L1 therapy.

Key highlights from the clinical data presentation include:

Efficacy results from the combination of SD-101 and pembrolizumab in confirmed PD-1 resistant or refractory patients demonstrated an 19.4% ORR in the SD-101 2 mg/lesion group and a 13.3% ORR in the SD-101 8 mg/lesion group
Responses were observed in SD-101 injected and non-injected lesions (including liver and lung metastases)
Responses and disease control were observed in BRAF mutant or wild type tumors
Biomarker data demonstrate that SD-101 added to pembrolizumab significantly changes the tumor microenvironment of patients that previously failed PD-1 blockade including the infiltration of activated T cells, NK cells, and B cells
The combination of SD-101 and pembrolizumab was well tolerated, consistent with previous reports
º No evidence of an increased incidence or severity of AEs over pembrolizumab monotherapy
º No increase in immune-related AEs over pembrolizumab monotherapy
º AEs associated with SD-101 were mainly mild to moderate injection-site reactions and flu-like symptoms that were manageable with over-the-counter medications
In addition, a poster titled: "Overcoming genetically based resistance mechanisms to PD-1 blockade" (Abstract No: 2584) was presented. The goal of the preclinical study was to assess mechanism-based strategies to overcome resistance to anti-PD1 therapy. Results demonstrated that even in the extreme setting of genetic resistance to PD-1 blockade by JAK1/2 LoF, resistance can be overcome by SD-101, a TLR9 agonist.

About SYNERGY-001 (KEYNOTE-184)
SYNERGY-001, previously referred to as MEL-01, is a Phase 1b/2 SYNERGY-001/KEYNOTE-184 trial in combination with KEYTRUDA which includes patients with histologically or cytologically confirmed unresectable Stage IIIC/IV melanoma. The primary endpoint of the trial is objective response rate assessed by RECIST v1.1. The secondary endpoints are safety and tolerability, progression-free survival and duration of response, with an exploratory endpoint of immunophenotype of the tumor microenvironment.

About SD-101
SD-101 is a proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. Dynavax is evaluating SD-101 in several clinical studies to assess its safety and activity, including a Phase 2 study in combination with KEYTRUDA (pembrolizumab) in advanced melanoma and metastatic or recurrent head and neck squamous cell cancer in collaboration with Merck, and in high risk breast cancer in collaboration with I-SPY 2. Dynavax maintains all commercial rights to SD-101.

On June 3, 2019 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of novel cancer therapies reported clinical updates from the Company’s ongoing first- and second-line trials in patients with MGMT-unmethylated glioblastoma multiforme (GBM) at a key opinion leader (KOL) forum focused on brain tumors and the role of VAL-083 to address the unmet medical need in GBM during the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, IL (Press release, DelMar Pharmaceuticals, JUN 3, 2019, View Source;and-second-line-trials-in-patients-with-mgmt-unmethylated-glioblastoma-at-a-key-opinion-leader-forum-during-the-american-society-of-clinical-oncology-asco-annual-meeting [SID1234536806]).

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At the KOL forum, the Company provided an update on the ongoing Phase 1/2 clinical study investigating the front line treatment of VAL-083 with radiation therapy in newly diagnosed MGMT-unmethylated GBM. This trial is being conducted at the Sun Yat-sen University Cancer Center (SYSUCC) in Guangzhou, China in collaboration with Guangxi Wuzhou Pharmaceutical Company. The trial is designed to enroll up to 30 patients to determine if first-line therapy with VAL-083 treatment, in lieu of first-line temozolomide, improves progression free survival (PFS).

As of May 17, 2019, eighteen patients have been enrolled in the trial. Of these patients, fifteen have received their post-cycle 3 MRI and investigator assessment, and ten have received their post-cycle 7 MRI and investigator assessment. Two patients have not been on the study long enough to reach their first assessment, and one patient died before their first assessment. Assessments are based on the trial investigator’s clinical and radiologic assessment, according to the Response Assessment in NeuroOncology (RANO) criteria. For the fifteen patients who have received at least one assessment, eight patients were assessed with a best response of "Complete Response" (8/15, 53.3% CR) and seven patients were assessed with a best response of "Stable Disease" (7/15, 46.7% SD). Fourteen of the eighteen patients were still alive at the data cut-off date.

The Company also provided an update on the ongoing second-line Phase 2 clinical study of VAL-083 in patients with MGMT-unmethylated, Bevacizumab-naïve recurrent GBM. This study is being conducted in collaboration with The University of Texas MD Anderson Cancer Center (MDACC). This biomarker-driven trial (testing for MGMT methylation status) has been amended to enroll up to 83 patients (35 with a starting dose of 40 mg/m2; 48 with a starting dose of 30 mg/m2) to determine the potential of VAL-083 treatment to improve overall survival compared to historical reference control of 7.2 months with lomustine.

As of May 5, 2019, 51 patients have been enrolled, 35 patients at a starting dose of 40 mg/m2, and 16 patients at a starting dose of 30 mg/m2.
For the 47 patients who have been on study long enough to be assessed at the post-cycle 2 MRI:
9/35 (25.7%) patients initially receiving 40 mg/m2 exhibited "Stable Disease" per investigator assessment at the end of cycle 2
4/12 (33.3%) patients initially receiving 30 mg/m2 exhibited "Stable Disease" per investigator assessment at the end of cycle 2
Additionally, the study protocol has been amended to include enrollment of up to 24 newly-diagnosed GBM patients who have completed chemoradiation treatment with TMZ and received no subsequent TMZ maintenance therapy but will receive VAL-083 instead (Group 2). This Group has been included to explore whether earlier intervention with VAL-083 instead of TMZ maintenance therapy offers clinical benefit and extends the time to recurrence as compared to TMZ maintenance therapy.

Consistent with prior studies, myelosuppression (primarily thrombocytopenia and neutropenia) is the most common adverse event in both ongoing clinical trials.

"We are pleased with the progress to date with our two Phase 2 programs for VAL-083. In our view, these results support the preclinical and prior clinical efficacy that was observed in the MGMT-unmethylated GBM population. Additionally, we continue to view the 2017 revised NCCN guidelines for MGMT-unmethylated GBM patients quite favorably for VAL-083, which cautions against the use of temozolomide (TMZ) for this particular patient population. The MGMT-unmethylated patients represent over 60% of the GBM cases and the revised NCCN guidelines expand the therapeutic opportunity for VAL-083 to all major lines of GBM treatment from front-line and maintenance as well as second line (recurrent) GBM," commented Saiid Zarrabian, DelMar’s Chief Executive Officer.

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class", bifunctional DNA-targeting agent that introduces inter-strand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute (NCI). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance, including MGMT, in cancer cell models and animal studies. Further details regarding these studies can be found at:

View Source

VAL-083 has been granted orphan drug designations by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA