On April 27, 2020 AIVITA Biomedical, Inc., a biotechnology company specializing in innovative cell therapy applications, reported that updates from ongoing clinical trials in ovarian cancer and glioblastoma were presented as part of the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I (Press release, AIVITA Biomedical, APR 27, 2020, View Source [SID1234556649]).

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The presentation from Daniela Bota, MD, Ph.D., of the University of California, Irvine, and principal investigator of the Phase 2 clinical trial of AV-GBM-1 in newly diagnosed glioblastoma, included data obtained through March 2020. The study has completed enrollment, and the treatment has been well-tolerated to date with encouraging preliminary survival data.

The presentation from Lisa Abaid, MD, principal investigator of the Phase 2 clinical trial of AVOVA-1 in advanced ovarian cancer, showed the trial is progressing as planned and the treatment has been well-tolerated. Enrollment for the study continues for both tumor collection and randomization.

"We’re encouraged by the progress we’ve made in our clinical programs and the positive tolerability that our patient-specific cancer vaccines have shown so far," said Hans Keirstead, Ph.D., chief executive officer of AIVITA. "We look forward to completing enrollment in our Phase 2 ovarian cancer study and further explore the promising survival data we’ve seen in our Phase 2 glioblastoma study."

The presentations will be available on the AACR (Free AACR Whitepaper) website site at www.aacr.org.

About AIVITA’S Clinical Trials

OVARIAN CANCER

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous tumor-initiating cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial, patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the tumor-initiating cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70, and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITA’s tumor-initiating cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations, and (5) are about to initiate anti-PD1 monotherapy.

On April 27, 2020 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for its investigational drug mobocertinib (TAK-788) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy (Press release, Takeda, APR 27, 2020, View Source [SID1234556648]). There are currently no approved therapies designed to treat this specific form of NSCLC. Mobocertinib is a small-molecule tyrosine kinase inhibitor (TKI) designed to selectively target EGFR and human EGFR 2 (HER2) exon 20 insertion mutations.

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The Breakthrough Therapy Designation is based on the overall response rate (ORR) and the long-term benefit seen in patients who responded in a Phase 1/2 study evaluating the safety and efficacy of mobocertinib in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and have been previously treated with systemic chemotherapy. This signals a potential advancement in addressing the needs of patients for whom no targeted therapies exist and current treatment options provide limited benefit.

"We are pleased that the FDA has recognized the therapeutic potential mobocertinib offers for patients with EGFR exon 20 insertion-mutant NSCLC who are desperately in need of effective treatment options," said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. "At Takeda, we are committed to developing novel medicines for hard-to-treat diseases. Establishing Breakthrough Therapy Designation for mobocertinib is one step forward in our efforts to help change the current standard of care for this underserved population."

"Although most EGFR mutations can be targeted by currently available TKIs, people with exon 20 insertion mutations often suffer and feel forgotten since available EGFR inhibitors don’t work well in their cancer," said Jill Feldman, Lung Cancer Patient, Advocate, and Co-Founder of the EGFR Resisters. "We are excited by the potential this treatment has to extend the lives of people who have had no approved treatment options to target their disease."

Breakthrough Therapy Designation from the U.S. FDA is granted to accelerate the development and regulatory review of investigational drugs that are intended to treat serious or life-threatening ailments. Agents with this designation have shown preliminary clinical evidence that indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Takeda will present for the first time the development of mobocertinib, including the first public disclosure of the structure, during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I in a New Drugs on the Horizon session on Tuesday, April 28, from 11:14-11:34 a.m. ET.

About EGFR Exon 20 Insertion-Mutant NSCLC

NSCLC is the most common form of lung cancer, accounting for approximately 85% of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization.1,2 Patients with EGFR exon 20 insertion mutations make up only about 1-2% of patients with NSCLC.3,4 This disease carries a worse prognosis than other EGFR mutations because there are currently no FDA-approved therapies that target exon 20 mutations, and current EGFR TKIs and chemotherapy provide limited benefit for these patients.

About Mobocertinib (TAK-788)

Mobocertinib is a potent, small-molecule TKI specifically designed to selectively target EGFR and HER2 exon 20 insertion mutations. In 2019, the U.S. FDA granted mobocertinib Orphan Drug Designation for the treatment of lung cancer with HER2 mutations or EGFR mutations including exon 20 insertion mutations.

Results from the ongoing Phase 1/2 trial of mobocertinib, which is evaluating the efficacy and safety of mobocertinib at 160 mg once daily in previously treated patients with EGFR exon 20 insertions, showed mobocertinib yielded a median progression-free survival (PFS) of 7.3 months and a confirmed overall response rate (ORR) of 43% (n=12/28) in patients with locally advanced or metastatic EGFR exon 20 insertion-mutant NSCLC. The safety profile of mobocertinib was manageable (N= 72). The most common treatment-related adverse events (AEs) were diarrhea (85%), nausea (43%), rash (36%), vomiting (29%) and decreased appetite (25%). These results were presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

The mobocertinib development program began in the NSCLC population and is expected to expand to additional underserved populations in other tumor types. Mobocertinib is an investigational drug for which efficacy and safety have not been established.

Takeda in Lung Cancer

Takeda is dedicated to expanding treatment options in the ALK+ NSCLC and EGFR/HER2 insertion-mutant NSCLC treatment landscapes. Our comprehensive programs include the following clinical trials to continue to address unmet needs for people living with lung cancer:

Mobocertinib:

Phase 1/2 study evaluating the safety, pharmacokinetics and antitumor activity of oral EGFR/HER2 inhibitor mobocertinib in patients with NSCLC. This trial has completed enrollment.
Phase 2 EXCLAIM, pivotal extension cohort of the Phase 1/2 trial, which was designed to evaluate the efficacy and safety of mobocertinib at 160 mg once daily in previously treated patients with EGFR exon 20 insertion mutations. This trial has completed enrollment.
Phase 3 EXCLAIM-2, global, randomized study evaluating the efficacy of mobocertinib as a first-line treatment compared to platinum-based doublet chemotherapy in treatment-naïve patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
Phase 1, open-label, multicenter, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of mobocertinib in Japanese patients with locally advanced or metastatic NSCLC. This trial has completed enrollment.
Phase 2 J-EXCLAIM, open-label, multicenter, study evaluating the efficacy of mobocertinib as a first-line treatment in Japanese patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. This trial is now enrolling.
Phase 1, open-label, multicenter, drug-drug interaction study of mobocertinib and midazolam, a sensitive CYP3A substrate, in patients with advanced NSCLC. This trial is now enrolling.
ALUNBRIG, a next-generation TKI designed to target and inhibit ALK molecular alterations:

Phase 1/2 trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ALUNBRIG. This trial has completed enrollment.
Pivotal Phase 2 ALTA trial investigating the efficacy and safety of ALUNBRIG at two dosing regimens in patients with ALK+ locally advanced or metastatic NSCLC who had progressed on crizotinib. This trial has completed enrollment.
Phase 3 ALTA-1L, global, randomized trial assessing the efficacy and safety of ALUNBRIG in comparison to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. This trial has completed enrollment.
Phase 2 J-ALTA, single-arm, multicenter trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib. This trial has completed enrollment.
Phase 2 ALTA 2, global, single-arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib. This trial has completed enrollment.
Phase 3 ALTA 3, global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib. This trial is now enrolling.
For additional information on the mobocertinib and ALUNBRIG clinical trials, please visit www.clinicaltrials.gov.

Takeda’s Commitment to Oncology

Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.

On April 27, 2020 Novocure (NASDAQ: NVCR) reported that an abstract highlighting results from the EF-19 post-approval registry trial studying Optune for the treatment of recurrent GBM will be presented as a virtual poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting I, taking place April 27-28, 2020 (Press release, NovoCure, APR 27, 2020, View Source [SID1234556647]).

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The FDA-mandated EF-19 post-approval registry trial studied Optune as a monotherapy for the treatment of recurrent GBM in 192 patients compared to the 117 recurrent GBM patients who received best standard of care chemotherapy in Novocure’s EF-11 registration trial. Optune as monotherapy reduced the risk of death with fewer adverse events compared to best standard of care chemotherapy. For patients who received at least one course of therapy, Optune prolonged survival by a median 1.7 months. No new safety signals were noted. The EF-19 data confirm the effectiveness and safety of Optune as monotherapy and further strengthen Optune’s clinical profile in recurrent GBM.

The AACR (Free AACR Whitepaper) Virtual Annual Meeting I will feature a selection of high-impact proffered paper presentations in several clinical trial plenary sessions and clinical trial poster sessions, along with minisymposia featuring basic and translational science. The virtual meeting will be available free to everyone, although attendees will be asked to register to participate.

Details for the AACR (Free AACR Whitepaper) 2020 Virtual Meeting I presentations are as follows:

Title: EF-19 – A post-approval registry study of TTFields for the treatment of recurrent glioblastoma (GBM)
Lead author: Jay-Jiguang Zhu, University of Texas Health Science Center, Houston, TX
Poster #: CT211
Session: VPO.CT03. Phase III Clinical Trials
Date and Time: April 27, 2020 9:00 AM – 6:00 PM
URL: View Source!/9045/presentation/10714

Title: HEPANOVA: Interim safety analysis from a phase 2 study of Tumor Treating Fields (TTFields, 150 kHz) concomitant with sorafenib in advanced hepatocellular carcinoma (HCC)
Lead author: Eleni Gkika, University of Freiburg, Freiburg, Germany
Poster #: CT186
Session: VPO.CT02. Phase II Clinical Trials
Date and Time: April 27, 2020 9:00 AM – 6:00 PM
URL: View Source!/9045/presentation/10686

Title: Optimizing Tumor Treating Fields therapy for recurrent glioblastoma with targeted and individualized skull remodeling surgery. A multi-center randomized phase 2 trial
Lead author: Nikola Mikic, Aarhus University Hospital, Aarhus, Denmark
Poster #: CT184
Session: VPO.CT02. Phase II Clinical Trials
Date and Time: April 27, 2020 9:00 AM – 6:00 PM
URL: View Source!/9045/presentation/10684

Title: PriCoTTF trial: A phase I/II trial of TTFields prior and concomitant to radiotherapy in newly diagnosed glioblastoma
Lead author: Sied Kebir, University Hospital Essen, Essen, Germany
Poster #: CT106
Session: VPO.CT01. Phase I Clinical Trials
Date and Time: April 27, 2020 9:00 AM – 6:00 PM
URL: View Source!/9045/presentation/10605

Title: Final results for OptimalTTF-1: Optimizing Tumor Treating Fields with targeted skull remodeling surgery for first recurrence glioblastoma: Phase 1 trial
Lead author: Nikola Mikic, Aarhus University Hospital, Aarhus, Denmark
Poster #: CR103
Session: VPO.CT01. Phase I Clinical Trials
Date and Time: April 27, 2020 9:00 AM – 6:00 PM
URL: View Source!/9045/presentation/10602

About Optune

Optune is a noninvasive, antimitotic cancer treatment for GBM. Optune delivers Tumor Treating Fields to the region of the tumor.

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die. Tumor Treating Fields does not stimulate or heat tissue and targets dividing cancer cells of a specific size. Tumor Treating Fields causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. Tumor Treating Fields is approved in certain countries for the treatment of adults with GBM and in the U.S. for MPM, two of the most difficult cancer types to treat. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

Approved Indications

Optune is intended as a treatment for adult patients with histologically-confirmed GBM.

Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial GBM following maximal debulking surgery, and completion of radiation therapy together with concomitant standard of care chemotherapy.

For the treatment of recurrent GBM, Optune is indicated following histologically- or radiologically-confirmed recurrence in the supratentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.

Important Safety Information

Contraindications

Do not use Optune in patients with GBM with an implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune ineffective.

Use of Optune for GBM together with implanted electronic devices has not been tested and may lead to malfunctioning of the implanted device.

Do not use Optune for GBM in patients known to be sensitive to conductive hydrogels. Skin contact with the gel used with Optune may commonly cause increased redness and itching, and may rarely lead to severe allergic reactions such as shock and respiratory failure.

Warnings and Precautions

Optune can only be prescribed by a healthcare provider that has completed the required certification training provided by Novocure.

The most common (≥10%) adverse events involving Optune in combination with chemotherapy in patients with GBM were thrombocytopenia, nausea, constipation, vomiting, fatigue, convulsions, and depression.

The most common (≥10%) adverse events related to Optune treatment alone in patients with GBM were medical device site reaction and headache. Other less common adverse reactions were malaise, muscle twitching, and falls related to carrying the device.

If the patient has an underlying serious skin condition on the treated area, evaluate whether this may prevent or temporarily interfere with Optune treatment.

Do not prescribe Optune for patients that are pregnant, you think might be pregnant or are trying to get pregnant, as the safety and effectiveness of Optune in these populations have not been established.

On April 27, 2020 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has successfully completed the crucial pyrogenicity testing that is required by the U.S. Food and Drug Administration (FDA) of the encapsulation material used to manufacture PharmaCyte’s Cell-in-a-Box capsules (CypCaps) (Press release, PharmaCyte Biotech, APR 27, 2020, View Source [SID1234556645]). The capsules, which house live human cells, passed the test and are deemed non-pyrogenic.

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PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said of the completed pyrogenicity testing, "While we never doubted that the capsules would be pyrogen free, we are very pleased that this vital FDA-required study has been successfully completed. We continue to remain centrally focused on submitting an Investigational New Drug application (IND) to the FDA. To that end, our team works every single day to complete the necessary items that will allow PharmaCyte to submit an IND for its planned Phase 2b clinical trial in locally advanced, inoperable pancreatic cancer. Meanwhile, as each test and item are completed, our team of experts and consultants is diligently compiling the data from these completed items and creating our IND package in real time."

All medical products that are delivered to the body have to be pyrogen free. Pyrogens are fever inducing substances that can cause side effects and influenza-like symptoms. Substances produced by bacteria (endotoxins) can be pyrogens, but other nonbacterial substances can be pyrogenic too.

The Cell-in-a-Box encapsulation procedure uses starting materials that have been tested and shown to be endotoxin free. However, the encapsulation process and machinery used for production of PharmaCyte’s CypCaps might potentially introduce nonbacterial pyrogens into the material used to encapsulate the human cells. The United States Pharmacopeia1 as well as the FDA2 require that advanced therapeutic medicinal products like CypCaps have to be tested for pyrogens.

In order to comply with these regulatory requirements, PharmaCyte requested Austrianova to produce a dedicated batch of empty cGMP capsules for pyrogenicity testing. It was an involved and time-consuming process to engineer empty cGMP capsules for the pyrogenicity testing. Once the empty capsules were manufactured, they were sent to Nelson Labs in Salt Lake City, Utah, for testing. A protocol had to be developed for the unique test material that would be used in rabbits. The capsules were extracted in saline at 50C for 72 hours and the extract was then injected into rabbits. This was done in order to determine if the injected matrix caused a fever. The results of the study have just been released. PharmaCyte can make the long-awaited announcement that the capsules passed the test and are deemed non-pyrogenic.

1United States Pharmacopeia (USP), 2011

2U.S. Department of Health and Human Services Food and Drug Administration, Guidance for Industry Pyrogen and Endotoxins Testing, 2012

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced inoperable pancreatic cancer, we encourage you to watch the company’s documentary video complete with medical animations at: View Source

On April 27, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported that it will release its financial results for the first quarter ended March 31, 2020, after the close of market on Monday, May 11, 2020 (Press release, Castle Biosciences, APR 27, 2020, View Source [SID1234556644]).

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Company management will host a conference call and webcast to discuss its financial results and provide a corporate update at 4:30 p.m. Eastern time on the same day.

Conference Call and Webcast Details

A live webcast of the conference call can be accessed at View Source or via the webcast link on the Investor Relations page of the Company’s website, View Source Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until June 1, 2020.

To access the live conference call via phone, please dial 877-282-2581 from the United States and Canada, or +1 470-495-9479, internationally, at least 10 minutes prior to the start of the call, using the conference ID 5699079.

There will be a brief Question & Answer session following the corporate update.