On August 13, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the European Commission (EC) has approved variations to broaden the use of Imbruvica (ibrutinib) in two indications (Press release, Johnson & Johnson, AUG 13, 2019, View Source [SID1234538653]). This includes the use of ibrutinib in combination with obinutuzumab in adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and the use of ibrutinib plus rituximab for the treatment of adult patients with Waldenström’s macroglobulinemia (WM). The approval follows the Positive Opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) on 28 June 2019.

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"The data supporting both the CLL and WM approvals show significant improvements in progression free survival with the use of ibrutinib-based therapy versus the standard of care study comparators respectively," said Dr Alessandra Tedeschi, Medical Director, Department of Hematology, Niguarda Hospital, Milan, Italy, and investigator in both the iNNOVATE and iLLUMINATE studies. "These approvals therefore provide healthcare professionals with new chemotherapy-free options for patients with these complex blood cancers."

The approval in CLL was based on results from the Phase 3 iLLUMINATE (PCYC-1130) study, published in The Lancet Oncology, which investigated ibrutinib in combination with obinutuzumab versus chlorambucil plus obinutuzumab in patients with previously untreated CLL.1

In WM, the decision was based on data from the Phase 3 iNNOVATE (PCYC-1127) study, published in the New England Journal of Medicine.2 The study evaluated the efficacy and safety of ibrutinib in combination with rituximab, versus rituximab with placebo, in patients with previously untreated and relapsed/refractory WM.3

Additional information about both studies can be found at www.ClinicalTrials.gov (NCT02264574 and NCT02165397).4,5

"With five European Commission approvals in five years, this latest EC decision further extends the potential reach and impact ibrutinib can have for patients," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "We remain committed to a comprehensive clinical development programme for ibrutinib, including exploring its use in other combinations, to address the needs of more and more patients with B-cell malignancies."

Ibrutinib, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialised by Janssen Biotech, Inc., and Pharmacyclics LLC, an AbbVie company.

Dr Alessandra Tedeschi is co-investigator in both the iNNOVATE and iLLUMINATE studies. She was not compensated for any media work.

#ENDS#

About ibrutinib
Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B-cells.6 By blocking this BTK protein, ibrutinib decreases survival and migration of B lymphocytes, thereby delaying progression of the cancer.7

Ibrutinib is currently approved in Europe for:8

Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with obinutuzumab for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients
Ibrutinib is approved in more than 95 countries, and, to date, has been used to treat more than 158,000 patients worldwide across its approved indications.

The most common adverse reactions seen with ibrutinib include diarrhoea, neutropenia, haemorrhage (e.g., bruising), musculoskeletal pain, nausea, rash, and pyrexia.8

For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About chronic lymphocytic leukaemia
Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.9 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.10 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.11

The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

About Waldenström’s macroglobulinemia
Waldenström’s macroglobulinemia (WM) is a rare form of non-Hodgkin’s lymphoma (NHL).12 It causes overproduction of a protein called monoclonal immunoglobulin M (IgM) antibody, which causes a thickening of the blood.13 Incidence rates among men and women in Europe are approximately 7.3 and 4.2 per million persons, respectively.14 The causes of WM are unknown, with it typically affecting older adults and being slightly more common in men than women.12,14

On August 13, 2019 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported updated data from its ongoing Phase 1 clinical study of ripretinib, a broad-spectrum KIT and PDGFRα inhibitor, in patients with second-line through fourth-line plus gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, AUG 13, 2019, View Source [SID1234538652]).

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In a separate press release issued today, Deciphera announced positive top-line results from its INVICTUS pivotal Phase 3 clinical study supporting a potential new drug application (NDA) submission to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib. In addition to the INVICTUS data, Deciphera will also be submitting in its NDA supportive data from the ongoing Phase 1 clinical study, which will include the updated data from GIST patients at doses of >100mg of ripretinib. Additional results from the Phase 1 clinical study in these patients are expected to be presented at an upcoming medical meeting.

"We believe the updated data from our ongoing Phase 1 clinical study, with the additional six months of maturity from our last Phase 1 data cut-off, continue to support ripretinib’s potential across the broad range of KIT and PDGFRα mutations known to occur in patients with GIST following therapy with imatinib," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "In the updated data from the second-line cohort, we believe ripretinib has demonstrated encouraging clinical benefit based on the objective response rate, disease control rate and median progression free survival rates observed. These results strengthen our confidence in the INTRIGUE pivotal Phase 3 clinical study comparing ripretinib to sunitinib, the standard of care for patients receiving second-line treatment for GIST."

Updated Phase 1 Data

Updated data from 178 GIST patients receiving ripretinib at doses of >100mg daily are noted in the table below as of March 1, 2019. The table includes investigator-assessed objective response rate (ORR) by best response, disease control rate (DCR) and median progression free survival (mPFS), all of which were determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Line of Therapy(1)

Objective Response Rate by Best Response

Includes Unconfirmed

(Confirmed Only)

Disease Control Rate

at 3 Months

Median Progression Free Survival (mPFS)

Censored Patients for mPFS

Mean Treatment Duration(2)(3)

Second-Line (n=37)

30% (22%)

81%

42 weeks

38%

43 weeks

Third-Line (n=31)

23% (13%)

80%

40 weeks

32%

48 weeks

Fourth-Line (n=60)

15% (8%)

73%

30 weeks

30%

49 weeks

≥Fourth-Line (n=110)(4)

11% (7%)

66%

24 weeks

22%

41 weeks

(1) Overall number of patients (n=178) remains the same as prior data presented at ESMO (Free ESMO Whitepaper) 2018; based on additional data cleaning, one patient from each of 2nd line and 4th/≥4th line were reclassified as 3rd line patients; (2) Median treatment durations were: 2nd line = 44 weeks, 3rd line = 48 weeks, 4th line = 46 weeks and ≥4th line = 29 weeks; (3) Includes 60 patients who elected for intra-patient dose escalation from 150 mg QD to 150 mg BID; (4) Number of patients includes 60 patients from 4th line.

Ripretinib was generally well tolerated and the updated adverse events were consistent with previously presented Phase 1 data in patients with GIST. Grade 3 or 4 treatment-emergent adverse events (TEAEs) in >5% of patients were lipase increased (18%; n=33), anemia (11%; n=20), hypertension (7%; n=13) and abdominal pain (6%; n=11). 13% of patients (n=24) experienced TEAEs leading to study treatment discontinuation, 17% of patients (n=31) experienced TEAEs leading to dose reduction and 49% of patients (n=88) had TEAEs leading to study drug interruption.

Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss this announcement, as well as results from the INVICTUS Phase 3 clinical study, today, August 13, 2019 at 8:00 AM ET. To access the live call by phone please dial 866-930-5479 (domestic) or 409-216-0603 (international); the conference ID is 8859018. A live audio webcast of the event and accompanying slides may also be accessed through the "Investors" section of Deciphera’s website at www.deciphera.com. A replay of the webcast will be available for 30 days following the event.

About GIST

Gastrointestinal stromal tumor (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in European and other countries. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 75% to 80% of cases, or in PDGFRα kinase, representing approximately 5% to 10% of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.

About Ripretinib

Ripretinib is an investigational KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and other cancers. Ripretinib was specifically designed to improve the treatment of patients with GIST by inhibiting a broad spectrum of mutations in KIT and PDGFRα. Ripretinib is a KIT and PDGFRα inhibitor that inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (Mainland China, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.

About the INTRIGUE Phase 3 Study

The INTRIGUE Phase 3 clinical study is an interventional, randomized, global, multicenter, open-label study to evaluate the safety, tolerability and efficacy of ripretinib compared to sunitinib in patients with GIST previously treated with imatinib. This study was designed to provide evidence of clinical benefit to support regulatory approvals in second-line GIST patients in the United States, Europe and other major markets. Patients will be randomized 1:1 to either 150 mg of ripretinib once daily or 50 mg of sunitinib once daily for four weeks followed by two weeks without sunitinib. The primary efficacy endpoint is median progression-free survival (mPFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR) and Overall Survival (OS). See www.clinicaltrials.gov for further information (NCT03673501).

On August 13, 2019 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported positive top-line data from the INVICTUS pivotal Phase 3 clinical study of ripretinib, a broad-spectrum KIT and PDGFRα inhibitor, in patients with fourth-line and fourth-line plus gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, AUG 13, 2019, View Source [SID1234538651]).

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"There is a dire unmet need for new therapies that can deliver effective disease control for patients with advanced GIST who have failed currently approved treatment options," said Margaret von Mehren, MD, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. "These top-line data from a Phase 3, randomized, placebo-controlled study are highly impressive and suggest that ripretinib’s approach of targeting the broad spectrum of KIT and PDGFRα mutations known to drive GIST can significantly improve progression free survival in the most heavily pretreated patients. Particularly notable is the magnitude of benefit observed for overall survival in this study."

The INVICTUS Phase 3 clinical study is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. The INVICTUS study achieved its primary endpoint of improved PFS as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

In the INVICTUS study, ripretinib demonstrated a median PFS of 6.3 months (27.6 weeks) compared to 1.0 month (4.1 weeks) in the placebo arm and significantly reduced the risk of disease progression or death by 85% (HR of 0.15, p<0.0001) compared to placebo.

For the key secondary endpoint of objective response rate (ORR), as determined by blinded independent central radiologic review using modified RECIST version 1.1, ripretinib demonstrated an ORR of 9.4% compared with 0% for placebo (p-value=0.0504), which was not statistically significant. Ripretinib in this study also showed a clinically meaningful improvement over placebo in terms of the secondary endpoint overall survival (OS) (median OS 15.1 months vs. 6.6 months, HR = 0.36, nominal p-value=0.0004). Since statistical significance was not achieved for ORR, the hypothesis testing of OS was not formally performed. According to the pre-specified hierarchical testing procedure of the endpoints, the hypothesis testing of OS cannot be formally conducted unless the test of ORR is statistically significant. The OS data for the placebo arm includes patients taking placebo who, following progression, were crossed-over to ripretinib treatment.

Ripretinib was generally well tolerated and the adverse event results in INVICTUS were consistent with data from previously presented Phase 1 study results. Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurred in 42 (49%) patients on the ripretinib arm compared to 19 (44%) on the placebo arm. Grade 3 or 4 TEAEs >5% of patients in the ripretinib arm were anemia (9%; n=8), abdominal pain (7%; n=6) and hypertension (7%; n=6). Grade 3 or 4 TEAEs >5% of patients in the placebo arm were anemia (14%; n=6). The below table lists TEAEs >15% in the ripretinib arm compared to placebo.

INVICTUS Phase 3 Clinical Study

Treatment Emergent Adverse Event

Placebo

Ripretinib

(N=43)(1)

150mg
Daily

(N=85)(1)

Any event

42 (98

%)

84 (99

%)

Alopecia

2 (5

%)

44 (52

%)

Fatigue

10 (23

%)

36 (42

%)

Nausea

5 (12

%)

33 (39

%)

Abdominal pain

13 (30

%)

31 (36

%)

Constipation

8 (19

%)

29 (34

%)

Myalgia

5 (12

%)

27 (32

%)

Diarrhea

6 (14

%)

24 (28

%)

Decreased appetite

9 (21

%)

23 (27

%)

Palmar-plantar erythrodysaesthesia syndrome

0

18 (21

%)

Vomiting

3 (7

%)

18 (21

%)

Headache

2 (5

%)

16 (19

%)

Weight decreased

5 (12

%)

16 (19

%)

Arthralgia

2 (5

%)

15 (18

%)

Blood bilirubin increased

0

14 (16

%)

Oedema peripheral

3 (7

%)

14 (16

%)

Muscle spasms

2 (5

%)

13 (15

%)

Notes to table: (1) Safety population includes 128 patients. One patient was randomized to placebo but did not receive study drug.

"Today’s announcement represents a significant milestone in our mission to deliver important new medicines for the treatment of cancer," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "On behalf of the entire Deciphera team, I would like to thank the patients, their caregivers and the healthcare professionals who participated in the INVICTUS study. The data from INVICTUS reinforce our belief that ripretinib has the potential to transform the treatment of GIST, and our focus now turns to working closely with the FDA as they evaluate ripretinib for those patients with GIST who, having failed all currently approved therapies, are in desperate need of a treatment option."

Based on the positive INVICTUS data, the Company expects to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.

Additional results from the INVICTUS Phase 3 clinical study are expected to be presented at an upcoming medical meeting.

Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss the results of the INVICTUS Phase 3 clinical study today, August 13, 2019 at 8:00 AM ET. To access the live call by phone please dial 866-930-5479 (domestic) or 409-216-0603 (international); the conference ID is 8859018. A live audio webcast of the event and accompanying slides may also be accessed through the "Investors" section of Deciphera’s website at www.deciphera.com. A replay of the webcast will be available for 30 days following the event.

About the INVICTUS Phase 3 Study

The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. This study was designed to provide evidence of clinical benefit in fourth-line and fourth-line plus patients with GIST that would be required to secure a regulatory approval. Patients were randomized 2:1 to either 150 mg of ripretinib or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR), Time to Tumor Progression (TTP) and Overall Survival (OS). See www.clinicaltrials.gov for further information (NCT03353753).

About GIST

Gastrointestinal stromal tumor (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in European and other countries. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 75% to 80% of cases, or in PDGFRα kinase, representing approximately 5% to 10% of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.

About Ripretinib

Ripretinib is an investigational KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and other cancers. Ripretinib was specifically designed to improve the treatment of patients with GIST by inhibiting a broad spectrum of mutations in KIT and PDGFRα. Ripretinib is a KIT and PDGFRα inhibitor that inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (Mainland China, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.

On August 13, 2019 Schrödinger reported an expansion of its computational design collaboration with Morphic Therapeutic ("Morphic"), a biotechnology company focused on developing a new class of oral small-molecule integrin-targeted therapeutics that Schrödinger co-founded with Harvard Professor Timothy Springer, Ph.D., and Polaris Partners (Press release, Schrodinger, AUG 13, 2019, View Source [SID1234538650]). The expanded agreement, signed in May 2019, extends the partnership to discover and design therapeutic compounds leveraging Schrödinger’s industry-leading computational platform. Under the terms of the amended agreement, Schrödinger will receive research funding as well as milestone payments and licensing royalties on candidate compounds that emerge from the collaboration.

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Through their partnership, Morphic and Schrödinger have accelerated the discovery and design of potent and selective integrin inhibitors and activators targeting serious chronic diseases, including autoimmune, cardiovascular, and metabolic diseases, fibrosis, and cancer. Schrödinger technology informs Morphic’s integrin technology, or MInT Platform, which leverages Morphic’s unique understanding of integrin structure and biology to develop a broad pipeline of novel product candidates designed to achieve the potency, high selectivity, and pharmaceutical properties required for oral administration.

"This collaboration brings together Morphic’s unparalleled insights into integrins and our proven, computational physics-based approaches to discovering and optimizing compound design. We’re excited to keep building on the momentum of our partnership, and we’ve seen tremendous validation for this approach through Morphic’s continued maturation, including its collaborations with large pharmaceutical companies and its recent initial public offering," said Ramy Farid, Ph.D., Schrödinger’s Chief Executive Officer. "Extending our partnership will allow us to broaden our pipeline as we work together to tackle serious diseases with high unmet need."

On August 13, 2019 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of novel cancer therapies, reported an update on the first 20 patients enrolled in its ongoing Phase 2 clinical study investigating the first-line treatment of VAL-083 in combination with radiation therapy in newly-diagnosed, MGMT-unmethylated GBM (Press release, DelMar Pharmaceuticals, AUG 13, 2019, View Source [SID1234538649]).

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As of August 1, 2019, 17 of the first 20 enrolled patients have received at least their first assessment (two patients have not been enrolled long enough to receive their first assessment and one patient died before their first assessment). "Best Overall Response" for these patients per investigator assessment were:

Nine have been assessed as having achieved a complete response (CR) (9/17, or 53%)
Seven have been assessed with stable disease (SD), (7/17, or 41%)
One has been assessed as disease progression (PD) (1/17, or 6%)
Importantly, 16 of the 20 patients enrolled (80%) were still alive as of the August 1, 2019 data cut-off date. The Company recently announced the enrollment of the 20th patient into this trial.

Dr. David Reardon, clinical director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and Professor of Medicine at the Harvard Medical School, and Dr. John de Groot, Professor and Chairman ad interim in the Department of Neuro-Oncology at The University of Texas MD Anderson Cancer Center (MDACC), are considered key opinion leaders in the brain cancer field and currently serve as DelMar Scientific Advisory Board members. Dr. Reardon commented, "Both John and I agree that we desperately need something better to offer our patients and we feel that VAL-083 has some promise and potential."

Dr. Reardon added, "For a tumor such as GBM, which is intrinsically infiltrative and destructive in the brain, stabilization of disease is an important achievement."

Professor Zhong-ping Chen, Founder Chairman of the Department of Neurosurgery/Neuro-oncology at Sun Yat-sen University Cancer Center (SYSUCC), who is the study’s principal investigator, stated, "We are pleased to be leading this Phase 2 trial for first-line GBM treatment with DelMar, and are encouraged by the enhanced levels of tumor shrinkage and the complete responses we are observing after treatment with VAL-083 in combination with radiation. These preliminary data appear to support the premise that VAL-083 has the potential to provide a valuable treatment option for these patients. We look forward to completing full enrollment in the study as soon as possible."

This Phase 2 trial which is being conducted at SYSUCC in Guangzhou, China, and in collaboration with Guangxi Wuzhou Pharmaceutical Company, is designed to enroll up to 30 patients to determine whether first-line therapy with VAL-083 treatment improves progression free survival (PFS). The current standard of care is first-line temozolomide (TMZ) with radiation. Of the 20 patients enrolled, 17 (85%) have received their two-month (post-third cycle) MRI and investigator assessment, 13 (65%) have received their five-month MRI and investigator assessment, and seven (35%) have received their eight-month MRI and investigator assessment. Two patients (10%) have not been on the study long enough to reach their first assessment, and one patient (5%) 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.

Saiid Zarrabian, DelMar’s president and chief executive officer, noted, "We continue to be encouraged by these early results and look forward to the completion of enrollment for our two, late-stage, Phase 2 studies. These results support our optimism that VAL-083 may provide a better treatment option than currently available treatments."

This Phase 2 trial is a single-arm, open-label study testing VAL-083 in combination with standard radiotherapy in GBM patients who have an unmethylated promoter of the methylguanine DNA-methyltransferase (MGMT) gene. The clinical trial in newly-diagnosed GBM patients is designed to determine if first-line treatment with VAL-083 plus radiotherapy can provide improvements over the historical efficacy of standard of care TMZ plus radiotherapy. Efficacy will be measured based on tumor response to treatment, progression-free survival, progression-free survival at six months, and overall survival compared to historical results in the target population.

The Company also recently announced the initiation of an adjuvant arm to the MDACC study to provide early disease data on VAL-083. This arm will enroll up to 24 newly-diagnosed patients who have undergone surgery and chemoradiation with TMZ but will now receive VAL-083 in place of standard of care TMZ for adjuvant therapy. This arm is in addition to a trial arm treating patients with recurrent disease, administering VAL-083 in patients who have been heavily pre-treated with TMZ prior to disease recurrence. The recurrent arm will allow a total of 83 patients to be enrolled, and both arms are being conducted at MDACC.

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:

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