On October 17, 2019 ADC Therapeutics SA, a clinical-stage oncology-focused biotechnology company pioneering the development of highly potent and targeted antibody drug conjugates (ADCs) for patients suffering from hematological malignancies and solid tumors, reported that the first patients have been dosed in a 100-patient pivotal Phase 2 clinical trial evaluating the efficacy and safety of ADCT-301 (camidanlumab tesirine) in patients with relapsed or refractory Hodgkin lymphoma (HL) (Press release, ADC Therapeutics, OCT 17, 2019, View Source [SID1234596054]). The trial is intended to support the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA).

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Alex Herrera, MD, Assistant Professor, Department of Hematology/Hematopoietic Cell Transplantation at City of Hope Medical Center and an investigator for the trial, said, "Approximately 15 to 25 percent of the 16,500 patients diagnosed with HL each year in the U.S. and Europe have relapsed or refractory HL. While advances have been made in the treatment of HL, a significant unmet medical need remains in the relapsed or refractory HL patient population, especially patients who have progressed following treatment with other novel agents. I believe ADCT-301 has the potential to fill this important medical need."

The primary objective of the Phase 2, multi-center, open-label, single-arm clinical trial is to evaluate the efficacy of ADCT-301 in patients with relapsed or refractory HL, measured by overall response rate based on the 2014 Lugano Classification Criteria. Patients with pathologically confirmed relapsed or refractory HL who have failed three prior lines of therapy, including brentuximab vedotin and a checkpoint inhibitor approved for HL such as nivolumab or pembrolizumab, are eligible for enrollment in the clinical trial.

Jay Feingold, MD, PhD, Senior Vice President, Chief Medical Officer and Head of Oncology Clinical Development at ADC Therapeutics, said, "In our large Phase 1 clinical trial, ADCT-301 demonstrated an overall response rate of 86.5 percent in patients with HL at the dose we are using in the pivotal Phase 2 clinical trial, with more than half of those being complete responses. We look forward to continuing the evaluation of ADCT-301 in this pivotal Phase 2 trial and, if successful, submitting a BLA to the FDA for accelerated approval of ADCT-301 for the treatment of relapsed or refractory HL in patients who have failed or were intolerant to brentuximab vedotin and a checkpoint inhibitor approved for HL."

For more information about the pivotal Phase 2 clinical trial of ADCT-301, please visit View Source (identifier NCT04052997).

About ADCT-301

ADCT-301 (camidanlumab tesirine) is an antibody drug conjugate (ADC) composed of a human monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine. Once bound to a CD25-expressing tumor cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead killing the cell with an immunogenic cell death. The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells. The ADC also depletes CD25-positive regulatory T cells in the tumor environment. All of these properties of ADCT-301 may enhance immune-mediated anti-tumor activity. ADCT-301 is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (NCT04052997), as well as ongoing Phase 1a/1b clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma (NCT02432235) and a Phase 1b clinical trial in solid tumors (NCT03621982).

On October 17, 2019 Immunomic Therapeutics, Inc. reported a presentation at the Precision Lung Cancer World R&D Summit in Boston (Press release, Immunomic Therapeutics, OCT 17, 2019, View Source [SID1234542340]). On Tuesday, October 22, Business Development Advisor at Immunomic, Yan Su, will present a talk entitled "Current & Future Application of the UNITE Platform in Cancer Immunotherapy," highlighting Immunomic’s investigational UNiversal Intracellular Targeted Expression (UNITE) platform and its application in immuno-oncology.

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Immunomic’s UNITE technology platform has the potential to utilize the body’s natural biochemistry to develop a broad immune response, including antibody production, cytokine release and critical immunological memory, a method that could put UNITE at the crossroads of immunotherapies in a number of illnesses, including cancer. The investigational UNITE technology is currently being applied as a cancer immunotherapy in a Phase II clinical trial targeting glioblastoma multiforme (GBM). Su’s presentation will explore the broader potential of UNITE through discussion of the LAMP-based immunotherapy technology, VAC2. VAC2 is an allogeneic cancer immunotherapy being developed by Lineage Cell Therapeutics, Inc. in collaboration with Cancer Research UK and is currently in a Phase 1 clinical trial for treatment of non-small cell lung cancer. In addition, the presentation will discuss the potential application of the UNITE Platform in Cancer targeting shared neoantigens.

Who: Yan Su, Business Development Advisor at Immunomic Therapeutics, Inc.

What: Presentation on Current & Future Application of the UNITE Platform in Cancer Immunotherapy

When: Tuesday, October 22 at 4:00 p.m. ET

Where: Wyndham Boston Beacon Hill, 5 Blossom St., Boston, MA 02114

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein, an endogenous protein in humans, for immune processing and MHC-II presentation to helper T-cells. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach could put UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in Phase II clinical trials as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.

On October 17, 2019 Xcovery Holdings, Inc., an oncology-focused biopharmaceutical company, reported that ensartinib, the company’s lead drug candidate, demonstrated efficacy and safety in patients with crizotinib-refractory, anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC), including those with brain metastases (Press release, Xcovery, OCT 17, 2019, View Source [SID1234542341]). The peer-reviewed manuscript of the study, "Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial" was published online in The Lancet Respiratory Medicine.

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"These results from the ensartinib China registration trial are very encouraging. They support our ongoing global phase 3 efforts in evaluating ensartinib’s efficacy and safety in the first line setting," said Li Mao, M.D., Chief Executive Officer of Xcovery, "Our company is dedicated to developing drugs to help cancer patients and we believe ensartinib has the potential to be the best-in-class first line therapy for ALK-positive NSCLC patients."

The multicenter phase 2 registration study analyzed the efficacy and safety of ensartinib in ALK-positive NSCLC patients that failed prior crizotinib treatment. The study also explored the associations between ensartinib efficacy and crizotinib-resistant mutations.

Ensartinib showed very promising activity in patients with ALK-positive NSCLC whose disease had progressed on previous crizotinib therapy. 52% (95% CI 43–60) of patients had a systemic objective response, whereas 70% (53–83) had an intracranial objective response, as assessed by an independent review committee.

In the study, most treatment-related adverse events were grade 1 or 2 and low proportions of patients required dose modifications or discontinued. Ensartinib also demonstrated activity against a broad array of ALK mutations, including G1202R, G1269A, F1174, C1156Y, and T1151.

D. Ross Camidge, M.D., from the University Of Colorado Department Of Medicine provided the Editorial Comment for the Lancet published study. "The median progression-free survival associated with ensartinib (9.6 months) was remarkably similar to that reported for the same drug at the same dose in a separate US study (9.2 months)," noted Dr. Camidge. "Cross-trial comparison would suggest that ensartinib’s activity is thus likely to be similar, if not marginally superior, to that of alectinib."

"This data set supports ensartinib as a new option for ALK-positive NSCLC patients in a refractory setting," said Giovanni Selvaggi, M.D., Chief Medical Officer at Xcovery and co-author of the study. "The high efficacy against brain metastases and the encouraging signal in resistant mutations, including G1202R, make ensartinib a promising treatment in an area where there is still significant unmet medical need."

To view the article, please visit https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30252-8/fulltext.

For more information on the ensartinib phase 3 clinical trial, please visit clinicaltrials.gov.

About Ensartinib

Ensartinib (X-396) is a potent anaplastic lymphoma kinase (ALK) inhibitor currently in a global phase 3 trial for ALK-positive NSCLC in the first line.

On October 17, 2019 Penumbra, Inc. (NYSE: PEN) reported that it will host a conference call to discuss financial results for the third quarter 2019 after market close on Thursday, November 7, 2019 at 4:30 PM Eastern Time (Press release, Penumbra, OCT 17, 2019, View Source [SID1234542342]). A press release with third quarter 2019 financial results will be issued after market close that day.

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Webcast & Conference Call Information
The conference call can be accessed live over the phone by dialing (833) 227-5837 for domestic callers or (647) 689-4064 for international callers (conference id: 4746448), or the webcast can be accessed on the "Events" section under the "Investors" tab of the Company’s website at: www.penumbrainc.com. The webcast will be available on the Company’s website for at least two weeks following the completion of the call.

On October 17, 2019 AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo) reported that the US Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for [fam-] trastuzumab deruxtecan (DS-8201) and granted Priority Review (Press release, AstraZeneca, OCT 17, 2019, View Source [SID1234542326]).

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The Prescription Drug User Fee Act (PDUFA) date for trastuzumab deruxtecan, a HER2-targeting antibody drug conjugate (ADC) and potential new medicine for the treatment of HER2-positive metastatic breast cancer, is set for the second quarter of 2020.

José Baselga, Executive Vice President, Oncology R&D, said: "Trastuzumab deruxtecan has the potential to transform the treatment landscape for patients with HER2-positive metastatic breast cancer who have limited treatment options today. This Priority Review draws on the strength and the consistency of results seen in the Phase I and Phase II trials and is a critical step on the journey to deliver this potential new medicine to patients."

Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: "We are pleased that the FDA has accepted the application and granted Priority Review, as we believe trastuzumab deruxtecan has the potential to redefine the treatment of patients with HER2-positive metastatic breast cancer. Following the recent regulatory submission in Japan, we look forward to working closely with regulatory authorities to bring trastuzumab deruxtecan to patients in the US and Japan as soon as possible."

Trastuzumab deruxtecan was previously granted US FDA Breakthrough Therapy Designation and Fast Track designation. The BLA is based on the combination of data from the Phase I trial published in The Lancet Oncology and the pivotal Phase II DESTINY-Breast01 trial.1 The response rate observed in DESTINY-Breast01, as assessed by an independent review committee, validated the clinical activity observed in the Phase I trial. Detailed data from DESTINY-Breast01 will be presented at the forthcoming San Antonio Breast Cancer Symposium in December.

About HER2

HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poorer prognosis in breast cancer patients.2 To be considered HER2-positive, tumour cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridisation (FISH). IHC test results are reported as: 0, IHC 1+, IHC 2+, or IHC 3+.2 A finding of IHC 3+ and/or FISH amplification is considered positive.2

About HER2-positive breast cancer

Approximately one in five breast cancers are HER2-positive.3,4 Despite recent improvements and approvals of new medicines, there remains significant clinical needs for patients with advanced HER2-positive metastatic breast cancer.5,6 This disease remains incurable with patients eventually progressing after available treatments.5,6 Additionally, there are currently no approved HER2-targeted medicines for HER2 FISH negative, IHC 2+ or IHC 1+ tumours.

About DESTINY-Breast01

DESTINY-Breast01 is a pivotal Phase II, open-label, global, multicentre, two-part trial evaluating the safety and efficacy of trastuzumab deruxtecan in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine. The primary endpoint of the trial is objective response rate, as determined by independent central review. Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival. Enrolment into DESTINY-Breast01 was completed in September 2018 with 253 patients at more than 100 sites across North America, Europe, Japan and other countries in Asia.

The safety and tolerability profile of trastuzumab deruxtecan in DESTINY-Breast01 was consistent with the Phase I trial data published in The Lancet Oncology, in which the most common adverse events (≥30 percent, any grade) included nausea, decreased appetite, vomiting, alopecia, fatigue, anaemia, diarrhoea and constipation. Cases of drug-related interstitial lung disease and pneumonitis, including grade 5 events, have also been reported in the clinical development programme.

About trastuzumab deruxtecan

Trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in US only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise and the most advanced programme in AstraZeneca’s ADC scientific platform. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

A comprehensive development programme is underway in North America, Europe and Asia, including five pivotal trials in HER2-expressing metastatic breast and gastric cancers, including a trial in patients with metastatic breast cancer and low levels of HER2 expression. Phase II trials are underway for HER2-expressing advanced colorectal cancer, as well as metastatic non-squamous HER2-overexpressing or HER2-mutated non-small cell lung cancer. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory submission of trastuzumab deruxtecan was recently made to Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of patients with HER2-positive metastatic breast cancer. It also received SAKIGAKE designation for the treatment of advanced HER2-positive gastric or gastroesophageal junction cancer by Japan’s MHLW.

About the collaboration between AstraZeneca and Daiichi Sankyo

In March 2019, AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise trastuzumab deruxtecan as a potential new medicine worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply in Japan.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.