On May 24, 2018 Merus N.V. (Nasdaq:MRUS), a clinicalstage immuno-oncology company developing innovative bispecific antibody therapeutics (Biclonics), reported that the first patient has been dosed in a Phase 1, first-in human clinical trial of MCLA158 in patients with solid tumors with an initial focus on metastatic colorectal cancer (Press release, Merus, MAY 24, 2018, View Source [SID1234532108]). The trial will be conducted in Europe, where several Clinical Trial Applications (CTAs) have been approved to date. The Company also announced the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for MCLA-158, which was accepted by the FDA in April 2018. With this acceptance, Merus plans to open additional sites for this trial in the United States.

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MCLA-158 is designed to bind to cancer stem cells expressing leucine-rich repeat-containing G proteincoupled receptor 5 (Lgr5) and epidermal growth factor receptors (EGFR). MCLA-158 was identified from a large library of bispecific antibodies targeting molecules belonging to the Wnt and receptor tyrosine kinase signaling pathways as part of work performed by the suppresSTEM consortium, a project that was funded by the European Union. Functional evaluation of patient-derived colorectal tumors, including those harboring RAS and/or PI3K mutations, demonstrated that MCLA-158 was more effective at inhibiting tumor growth and promoting apoptosis than an approved targeted therapy comparator for metastatic colorectal cancer, cetuximab. In preclinical studies, Merus also observed that the growth inhibitory activity of MCLA-158 was greater for colon tumors compared to normal colon tissue, consistent with its good safety profile in non-human primates.

"The commencement of our Phase 1 clinical trial of MCLA-158 is an important milestone for the advancement of our pipeline of bispecific antibodies obtained from our Biclonics technology platform," said Ton Logtenberg, Ph.D., Chief Executive Officer. "We believe MCLA-158 has the potential to address features that limit currently approved colorectal cancer-targeted therapies, including issues with offtarget toxicity and inability to target tumor stem cells, and thus, potentially treat a broader population of patients more effectively."

The Phase 1, open-label, multicenter clinical trial of MCLA-158 consists of two parts, a dose escalation and a dose expansion. The dose escalation part is intended to determine the appropriate dose of MCLA158. The dose expansion part will evaluate the safety and tolerability of the defined dose of MCLA-158 in patients with solid tumors. The dose escalation and expansion parts of the trial will also examine the preliminary antitumor activity of single-agent MCLA-158.

On May 24, 2018 VBL Therapeutics (Nasdaq:VBLT), a clinical-stage biotechnology company focused on the discovery, development and commercialization of first-in-class treatments for cancer, reported that the Company will present an update on the OVAL Phase 3 trial of VB-111 in platinum-resistant ovarian cancer at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting, to be held June 1-5 in Chicago, Illinois (Press release, VBL Therapeutics, MAY 24, 2018, View Source [SID1234526889]). In addition the Company will present data on its novel MOSPD2 program at the 2018 BIO International Convention, to be held June 4-7, 2018 in Boston.

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2018 ASCO (Free ASCO Whitepaper) Annual Meeting – Presentation Details

Title: Clinical trial in progress: A study of VB-111 combined with paclitaxel vs. paclitaxel for treatment of recurrent platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Abstract: TPS5609
Session Title: Gynecologic Cancer
Date: June 4, 2018
Time: 1:15 PM-4:45 PM CDT
Location: Hall A
Poster Board: #331b
Presenter: Dr. Richard T. Penson, M.D.,MRCP, associate professor of Medicine, Harvard Medical School, clinical director of Medical Gynecologic Oncology, Massachusetts General Hospital
2018 BIO International Convention – Presentation Details

Date: Tuesday, June 5, 2018
Time: 2:45 pm EDT
Presentation Room: Theater 1
Location: Boston Convention & Exhibition Center
Webcast: Bio International Webcast Link
About VB-111 (ofranergene obadenovec)
VB-111, a potential first-in-class anticancer therapeutic candidate, is the Company’s lead oncology product currently being studied in a Phase 3 trial for ovarian cancer. VB-111 has received an Orphan Designation for the treatment of ovarian cancer by the European Medicines Agency (EMA). At the 2016 ASCO (Free ASCO Whitepaper), the Company presented data in platinum-resistant ovarian cancer, demonstrating a meaningful and significant increase in overall survival with VB-111 given in combination with chemotherapy (810 days vs. 172 days, p=0.042), along with a 60% durable CA-125 response rate—approximately two times the historical response observed with bevacizumab (Avastin) plus chemotherapy in ovarian cancer. The OVAL study is conducted in collaboration with the Gynecologic Oncology Group (GOG) Foundation, Inc., a leading organization for research excellence in the field of gynecologic malignancies.

About MOSPD2
MOSPD2 is a novel tumor-related target identified by VBL that may be used as a marker for selective targeting of several types of tumors. Research conducted by VBL has shown that MOSPD2 is a novel membrane protein found on tumor cells that is present when they start invading tissues or creating metastatic lesions. The Company believes that targeting of MOSPD2 may have several therapeutic applications, including inhibition of tumor cell metastases and targeting of MOSPD2-positive tumor cells. There are also potential applications in the inhibition of monocyte migration in chronic inflammatory conditions. VBL is developing the VB-600 series of pipeline candidates towards these applications.

On May 24, 2018 Cotinga Pharmaceuticals Inc. (TSX-V:COT) (OTCQB:COTQF) ("Cotinga" or the "Company"), a clinical-stage pharmaceutical company advancing a pipeline of targeted therapies for the treatment of cancer, reported the clearance of a protocol amendment for its ongoing clinical trial of COTI-2 (Press release, Cotinga, MAY 24, 2018, https://globenewswire.com/news-release/2018/05/24/1511485/0/en/Cotinga-Pharmaceuticals-Announces-FDA-Clearance-of-Significant-Protocol-Changes-for-COTI-2-Clinical-Program.html [SID1234533153]). The multi-part protocol amendment expands the trial to evaluate COTI-2 as a combination therapy in a wide spectrum of cancers. The Company will initially evaluate COTI-2 combined with standard of care cisplatin in up to 30 patients with any of ovarian, fallopian tube, primary peritoneal, endometrial, cervical, lung, pancreatic or colorectal cancer, or head and neck squamous cell carcinoma.

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"Following extensive work with our academic collaborators and the FDA, we are pleased to expand the ongoing clinical trial of our lead asset, COTI-2, to evaluate its potential as a combination therapy in various cancers with severe unmet medical need," said Alison Silva, President and Chief Executive Officer. "We have already begun to roll-out the initial part of the protocol amendment for our sites at MD Anderson Cancer Center and Northwestern University, and we will continue to work closely with investigators to ensure the process runs smoothly. We look forward to announcing the first patient dosed with combination therapy and providing updates as we continue to advance the clinical development of COTI-2."

Phase 1b/2a Trial of COTI-2
The ongoing trial of COTI-2 will now focus on evaluating COTI-2 as a combination therapy for the potential treatment of a wide spectrum of cancers. In 2017, the Company announced top-line data from the gynecological malignancies arm of the trial demonstrating monotherapy with COTI-2 was generally safe and well-tolerated. Monotherapy with COTI-2 also exhibited an encouraging pharmacokinetic/pharmacodynamic profile and signals of efficacy.

The current protocol amendment being implemented by the Company in May 2018 expands the ongoing trial to evaluate COTI-2 in combination with various standard of care chemotherapy regimens in a wide spectrum of cancers.

This protocol amendment evaluates COTI-2 combined with standard of care cisplatin in up to 30 patients with any of the following malignancies: ovarian, fallopian tube, primary peritoneal, endometrial, cervical, lung, pancreatic or colorectal cancer, or head and neck squamous cell carcinoma. Patients in this dose finding study will be given a 60 mg/m2 IV dose of cisplatin every three weeks in combination with an oral dose of COTI-2 five days per week. Up to five COTI-2 dose levels will be evaluated ranging from 0.5 mg/kg to 3.5 mg/kg and patient assessments will occur every eight weeks. Primary outcome measures will evaluate safety and tolerability and determine the maximum tolerated dose and recommended Phase 2 dose for COTI-2 as a combination therapy. Secondary and exploratory outcome measures will evaluate pharmacokinetics and various signals of efficacy. Additional details on the protocol amendment are available on clinicaltrials.gov.

On May 24, 2018 AstraZeneca and MedImmune,reported its global biologics research and development arm, head to the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, US, 1-5 June 2018, with an expanded portfolio in Oncology (Press release, AstraZeneca, MAY 24, 2018, View Source [SID1234526873]).

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Having achieved 16 regulatory approvals across major markets (US, EU, Japan and China), AstraZeneca will be sharing its R&D momentum at ASCO (Free ASCO Whitepaper) with seven "Best of ASCO (Free ASCO Whitepaper)" presentations and 14 oral presentations from a total of 91 accepted abstracts. These presentations will showcase AstraZeneca’s four scientific platforms: Immuno-Oncology (IO), DNA Damage Response (DDR), Anti-Drug Conjugates (ADCs), and Tumour Drivers and Resistance.

Dave Fredrickson, Executive Vice President, Head of Oncology Business Unit said: "In just four years, AstraZeneca has launched four innovative medicines to treat serious cancers: Lynparza in ovarian and metastatic breast cancers, Imfinzi in bladder cancer and unresectable stage III non-small cell lung cancer, Tagrisso in epidermal growth factor receptor-mutated non-small cell lung cancer and Calquence as the first haematology medicine in mantle cell lymphoma. At this year’s ASCO (Free ASCO Whitepaper) meeting, the Company will showcase a strong portfolio, a rich pipeline and a focus on impactful industry partnerships which will fuel continued advances in oncology and haematology."

Lynparza: Study 08 data in prostate cancer

An oral presentation of Study 08, evaluating Lynparza in combination with abiraterone in metastatic castration-resistant prostate cancer, will highlight the potential of PARP inhibition beyond ovarian and metastatic breast cancers, regardless of homologous recombination repair mutation status (Abstract #5003). Lynparza is being jointly developed and commercialised by AstraZeneca and MSD, known as Merck in the US and Canada.

Progress in haematology

Response rates and safety data from the Phase III (‘1053’) multicentre trial of the investigational ADC moxetumomab pasudotox in relapsed or refractory hairy cell leukaemia (HCL) patients (Abstract #7004) will be presented. The FDA has granted the moxetumomab pasudotox Biologics License Application Priority Review status; if approved, it will be a first-in-class treatment for patients with relapsed refractory HCL.

New data will also be presented for Calquence (acalabrutinib), a selective Bruton’s tyrosine kinase (BTK) inhibitor and AstraZeneca’s first medicine approved in haematology. Findings will be shared in an oral presentation of the Phase II clinical trial (WM-001) of patients with treatment-naïve, relapsed or refractory Waldenström macroglobulinemia (Abstract #7501).

Investigator-led studies highlight the value of collaboration in new areas of unmet need

AstraZeneca’s broad network of industry and academic partners is broadening exploration of the company’s pipeline into additional tumour types where unmet patient needs remain. The US National Cancer Institute (NCI), a division of the US National Institutes of Health (NIH), will present Phase II data from the ongoing SPRINT trial evaluating MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886), a potential new medicine within the AstraZeneca and MSD partnership, in paediatric patients with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (Abstract #10503). The SPRINT abstract was awarded the 2018 Conquer Cancer Foundation of ASCO (Free ASCO Whitepaper)/Bradley Stuart Beller Special Merit Award.

Additional investigator-sponsored research includes a late-breaking oral presentation on the Phase II GeparNuevo trial of neoadjuvant treatment with Imfinzi (durvalumab) in triple-negative breast cancer (TNBC). AstraZeneca initiated this study alongside the German Breast Group and Celgene (Abstract #104), and the DREAM Phase II trial of Imfinzi in combination with chemotherapy in first-line mesothelioma (Abstract #8503).

Early pipeline powered by combinations

AstraZeneca’s early-stage pipeline will also be showcased at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting with 39 abstracts highlighting its breadth and depth.

In an oral presentation, data from PAKT, a Phase II trial of capivasertib (AZD5363), a highly selective, oral, AKT inhibitor with paclitaxel, demonstrate the impact of this combination on progression free survival and overall survival in previously untreated, metastatic TNBC (Abstract #1007). This trial was sponsored and led by Queen Mary University London and the Bart’s Cancer Institute.

Additionally, progress against PD(L)-1 insensitive tumours will be highlighted with presentations of two first-in-human studies from the early IO pipeline; the investigational anti-CD73 human monoclonal antibody oleclumab alone or in combination with Imfinzi in advanced pancreatic cancer and colorectal cancer (Abstract #4123), and monalizumab (NKG2A) in combination with Imfinzi in patients with metastatic microsatellite-stable colorectal cancer (Abstract #3540).

Key AstraZeneca/MedImmune presentations at ASCO (Free ASCO Whitepaper) 2018
Lead author

Abstract title

Presentation details

DNA Damage Response

Clarke N

Olaparib combined with abiraterone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): a randomized Phase II trial

Oral

Genitourinary (Prostate) Cancer

Monday 4th June, 15:00-18:00

Presentation Time: 16:00-16:12

Location: Hall D1

Abstract #5003

Westin SN

Phase 1 trial of olaparib (PARP inhibitor) and vistusertib (mTORC 1/2 inhibitor) in recurrent endometrial, ovarian and triple-negative breast cancer

Oral

Gynecologic Cancer

Tuesday 5th June, 10:57-11:09

Location: S100a

Abstract #5504

Johnson M

A phase I, open-label, multicenter dose escalation study to assess the safety, tolerability, and pharmacokinetics of AZD2811 nanoparticle in patients with advanced solid tumors

Poster

Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics

Monday 4th June, 08:00-11:30

Abstract #2592

Poster #418

Heymach J

An open-label, multidrug, biomarker-directed, multicentre phase II umbrella study in patients with non-small cell lung cancer, who progressed on an anti-PD-1/PD-L1 containing therapy (HUDSON)

Poster

Developmental Therapeutics – Immunotherapy

Monday 4th June, 08:00-11:30

Location: Hall A

Abstract #TPS3120

Poster #324b

Immuno-Oncology

Loibl S

Randomized Phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple-negative breast cancer (TNBC)

Oral

Compelling Combinations: Raising the Bar With Immunotherapy

Sunday 3rd June, 09:45-11:15

Presentation Time: 09:57-10:09

Location: Hall D1

Abstract #104

Nowak AK

DREAM: A phase II study of durvalumab with first line chemotherapy in mesothelioma—First results.

Oral

Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Monday 4th June, 08:00-11:00

Presentation Time: 09:00-09:12

Location: Hall B1

Abstract #8503

Garassino MC

Durvalumab in ≥3rd-line advanced NSCLC: updated results from the Phase 2 ATLANTIC study

Poster

Lung Cancer—Non-Small Cell Metastatic

Sunday 3rd June, 08:00-11:30

Location: Hall A

Abstract #9058

Poster #381

Segal NH

First-in-human dose escalation of monalizumab plus durvalumab, with expansion in patients with metastatic microsatellite-stable colorectal cancer

Poster

Gastrointestinal (Colorectal) Cancer

Sunday 3rd June, 08:00-11:30

Location: Hall A

Abstract #3540

Poster #33

Overman M

Safety, Efficacy and Pharmacodynamics (PD) of MEDI9447 (oleclumab) Alone or in Combination with Durvalumab in Advanced Pancreatic Cancer (panc) or Colorectal Cancer (CRC)

Poster

Gastrointestinal (Noncolorectal) Cancer

Sunday 3rd June, 08:00-11:30

Location: Hall A

Abstract #4123

Poster #312

Tumour Drivers & Resistance

Gross A

SPRINT: Phase II study of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) in children with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN)

Oral

Pediatric Oncology I

Saturday 2nd June, 15:00-18:00

Presentation Time: 16:00-16:12

Location: S504

Abstract #10503

Owen R

Acalabrutinib in patients (pts) with Waldenström macroglobulinemia (WM)

Oral

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Sunday 3rd June, 09:45-12:45

Presentation Time: 09:57-10:09

Abstract #7501

Schmid P

AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): a randomised, double-blind, placebo-controlled, phase II trial

Oral

Breast Cancer – Metastatic

Sunday 3rd June, 08:00-11:00

Presentation Time: 10:12-10:24

Location: Hall D2

Abstract #1007

Antibody-Drug Conjugates

Kreitman R

Moxetumomab pasudotox in heavily pretreated patients with relapsed/refractory hairy cell leukemia: results of a pivotal international study

Oral

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Saturday 2nd June, 15:00-18:00

Discussion Time: 16:12-16:24

Location: E450

Abstract #7004

On May 24, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported that topline results from the Phase III study of Arzerra (ofatumumab) plus bendamustine did not meet the primary endpoint of improved progression-free survival (PFS) in patients with indolent B-cell non-Hodgkin’s lymphoma (iNHL) who were unresponsive to rituximab or a rituximab-containing regimen, compared to those given bendamustine alone (Press release, Genmab, MAY 24, 2018, View Source [SID1234526894]). The safety profile observed in this study was consistent with that observed in other trials of ofatumumab and no new safety signals were observed.

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"We are disappointed that the ofatumumab treatment regimen did not meet the primary endpoint in this trial. The completion of this Phase III study, which began in 2010, would not have been possible without the generous participation of the patients and their families, and we are most grateful for this. The full data will be submitted for publication at a future medical conference and we hope that these will provide a better understanding of this result," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The results from this Phase III study do not impact any other ongoing studies with ofatumumab.

About the study (COMPLEMENT A+B)
The study is an open-label, two-arm, randomized, Phase III study that included 346 patients with indolent B-cell non-Hodgkin’s lymphoma who were unresponsive to rituximab or a rituximab-containing regimen. Patients in the study were randomized 1:1 to treatment with up to eight cycles of bendamustine given in combination with 12 doses of ofatumumab (1,000 mg) or up to eight cycles with bendamustine alone. The primary endpoint of the study was PFS.

Ofatumumab is not approved for the treatment of indolent non-Hodgkin’s Lymphoma.

About Ofatumumab (Arzerra)
Ofatumumab is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of normal B lymphocytes and on B cell malignancies (including chronic lymphocytic leukemia and non-Hodgkin’s lymphomas).

In the United States, Arzerra is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate, in combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL and for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. In the European Union, Arzerra is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy and in combination with fludarabine and cyclophosphamide for adult patients with relapsed CLL. In more than 60 countries worldwide, including the United States and EU member countries, Arzerra is also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab. On January 22, 2018, it was announced that Novartis intends to transition Arzerra for the treatment of CLL indications from commercial availability to limited availability via compassionate use programs in non-U.S. markets.