On August 24, 2020 Adlai Nortye Ltd. ("Adlai Nortye"), a global clinical-stage biopharmaceutical company reported that the first patient has been dosed in a phase 1b clinical trial (AN0025S0103) to evaluate AN0025, an investigational, potentially first in class oral EP4 antagonist, in combination with Merck’s KEYTRUDA (pembrolizumab) in patients with locally advanced/metastatic solid tumors (Press release, Adlai Nortye Biopharma, AUG 24, 2020, View Source [SID1234563957]).

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AN0025S0103 is an open-label, multicenter, phase 1b study in the U.S. and Europe to evaluate the safety and preliminary efficacy of AN0025 in combination with pembrolizumab in patients with locally advanced/metastatic tumors. It will include a dose-limiting toxicity (DLT) observation phase followed by an expansion phase. In the DLT phase, it will enroll patients with urothelial carcinoma of the bladder, or squamous or non-Squamous NSCLC, to assess safety and tolerability. This will be determined whether or not to move on to the expansion phase, which will enroll patients diagnosed with urothelial carcinoma, NSCLC, TNBC, Cervical cancer, and MSS CRC. The first patient was dosed at Huntsman Cancer Institute (HCI) at the University of Utah. In the U.S., the study is also enrolling patients from The University of Texas MD Anderson Cancer Center and The University of Virginia Cancer Center.

All enrolled patients will be treated with AN0025 and pembrolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent, or for a maximum of 35 cycles (approximately 2 years). The dose of Pembrolizumab will remain constant at 200 mg every 3 weeks (Q3W) for each dose level of AN0025 and in each cohort.

"In preclinical studies, AN0025 combined with radiotherapy, chemoradiotherapy and with immune checkpoint inhibitors demonstrated antitumor activity in different malignancies. We are optimistic that the combination of AN0025 (EP4 Antagonist) with KEYTRUDA could have meaningful clinical benefit in patients with locally advanced/metastatic solid tumors," said Dr. Lars Birgerson, CDO and CEO of Adlai Nortye USA. "This new combination may provide a new systemic treatment option for many cancer patients, including PD-1/PD-L1 treatment refractory or relapsed patients. We hope to bring innovative cancer treatments to patients with unmet medical needs, to help patients live longer and better."

About AN0025S0103

AN0025S0103 is an open-label, multicenter, phase 1b study to evaluate the safety and preliminary efficacy of AN0025 in combination with pembrolizumab in patients with locally advanced/metastatic tumors. It will include a dose-limiting toxicity observation phase followed by an expansion phase. All enrolled patients will be treated with AN0025 and Pembrolizumab until the patient experiences disease progression, unacceptable toxicity or withdraws consent, or for a maximum of 35 cycles (approximately 2 years). The dose of pembrolizumab will remain constant at 200 mg every 3 weeks (Q3W) for each dose level of AN0025 and in each cohort.

About AN0025 (EP4 Antagonist)

AN0025 (previously E7046) is an investigational, potentially first in class oral EP4 antagonist that blocks prostaglandin E2 from binding to its subtype 4 receptor (EP4) changing the immunosuppressive character of the tumor microenvironment. Based on preliminary results, it is well tolerated in patients with solid tumors. A Phase 1b study of AN0025 in combination with the standard of care in a neoadjuvant setting for locally advanced rectal cancer showed excellent results, with nearly 40% of patients not requiring surgery or achieving a complete pathological response in the post-surgical specimen in this study.

On August 23, 2020 Genomic Testing Cooperative (GTC) reported that it has launched a joint venture with Hackensack Meridian Health (HMH) that will analyze clinical samples from patients with a variety of different cancers (Press release, Genomic Testing Cooperative, AUG 23, 2020, View Source;utm_medium=rss&utm_campaign=genomic-testing-cooperative-aims-to-expand-clinical-commercial-ngs-access-with-co-op-model [SID1234564047]).

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The Irvine, California-based group is building separate reference labs at HMH’s John Theurer Cancer Center (JTCC) in Hackensack, New Jersey and at HMH’s JFK Medical Center in Edison, New Jersey, which will provide complete DNA and RNA profiling services to physicians and hospitals on the East Coast.

GTC CEO Maher Albitar, who previously served as chief medical officer at NeoGenomics, said that academic and small commercial labs often struggle to cover the costs of sequencing samples for clinical research projects. He hopes to minimize the costs of sequencing and improve access to expensive sequencing workflows by cooperating with labs across the US.

GTC’s "co-op" business model consists of two strategies, depending on the partner’s size and financial resources. Smaller labs that cannot afford high-end sequencing instruments send clinical samples to GTC’s CLIA-certified, CAP-approved lab in California, where the firm sequences the samples on its Illumina instruments. GTC then implements algorithms, based on deep-learning and artificial intelligence, to interpret the sequencing data.

For hematology and oncology groups at larger laboratories or hospitals, GTC instead establishes a wet lab with sequencing instruments in their facility to analyze data from inhouse NGS tests. Albitar highlighted that the final report is identical, whether the sequencing portion of the workflow is done at GTC or at the partner’s lab.

Depending on the size of the facility that GTC partners with, Albitar’s team can deliver DNA analysis results within seven days. If the collaborator wishes to include RNA data in the analysis, the firm can produce results in about 10 days.

"Because our partners have a vested interest in this process, we work collaboratively and [make it] less expensive," Albitar said. "For example, they give us access to their clinical data, which makes it easier to find indications, correlations, and validation for our assays than if we were to purchase samples with clinical data from diagnostic labs."

GTC currently offers nine cancer genomic profiling tests that its co-op partners can request, including a liquid biopsy assay developed by partner C2i Genomics. While declining to provide the number of tests that GTC has performed, Albitar said that the firm has seen a 30 percent growth in analyzed samples almost every month since launching in 2018.

Albitar argued that GTC can successfully lower overall sequencing costs that companies often encounter because it increases sample volume gathered from partners. He believes the firm’s model is the first that is based on cooperation, rather than competition, between companies.

"Instead of working in silos and competing with each other, I believe that clinical laboratories should collaborate with each other so that they can deliver better patient care," Albitar explained. "By [using] a collaborative structure, smaller laboratories can have access to the required expertise in NGS and direct access to [an] innovation pipeline in [a] costeffective manner."

While acknowledging that GTC’s services can potentially allow an interested partner to sequence samples for different disease-linked biomarkers, Albitar said that the co-op is currently focusing on sequencing cancer tumor and liquid biopsy samples.

GTC has filed three patents with the US Patent and Trademark Office related to RNA analysis and how RNA can be used for the prediction of clinical behavior of cancers. As part of the model, Albitar noted, every patent the group generates will be shared with the members of the co-op as well. He also highlighted that every member of the co-op has a say in the group’s current and future decisions.

HMH agreement
By signing a contract with HMH, which covers 17 different hospitals and more than 200 patient centers in New Jersey, GTC expects to offer complete DNA and RNA profiling to cancer patients in an efficient and cost-effective manner. The firm will also collaborate with HMH’s data company to get access to clinical data for developing new tests and applications of DNA and RNA sequencing.

Andre Goy, physician-in-chief of oncology at HMH, noted that the group will look at the impact of detected cancer signatures and refine decisions of patient care. For example, HMH clinicians will alter decisions for high-risk lymphoma patients with "standard morphology," who may instead need more intensive therapy. The workflow will also provide his team of clinicians potentially actionable results for rare or difficult-to-treat cancers.

GTC also aims to widen its network of reference labs for genomic testing by opening the facility at HMH to serve as a testing hub on the East Coast, while the California facility will serve the co-op’s interests on the West Coast. The lab will perform NGS testing before providing GTC with the data for downstream analysis.

Albitar noted that the new lab will allow sample collection from the entire health network, as well as support any of GTC’s co-op partners working to push their diagnostic product to the market. However, he emphasized that the facility will not be linked to any of the firm’s existing agreements, especially those related to collaborating oncology practice groups.

For example, Albitar pointed to GTC’s partnership with the JTCC from May, under which the team is building an additional sequencing lab to molecularly profile cancer samples. While the lab will collect cancer samples, the initial JTCC agreement restricted Albitar’s team from collecting them outside the Regional Cancer Care Associates (RCCA) network.

Instead, the new agreement with HMH will allow GTC to separately work with a higher number of physicians outside the RCCA network at HMH as part of the planned reference lab. Goy highlighted that the health network sees roughly 30,000 new cancer patients per year.

Previous collaborations
In addition to the HMH and JTCC joint ventures, GTC previously signed an agreement with C2i Genomics in January to help commercialize the firm’s liquid biopsy tests for solid tumor staging and monitoring. GTC also partnered with Cellgen Diagnostics in 2019 to offer companion diagnostic development for cancer immunotherapy developers.

GTC will use the HMH collaboration to help build a network of reference labs across the country. The firm will aggregate sequencing data from the network — which Albitar said will be standardized by applying the same methods and tools — into a database that it hopes will form the basis of future research for improving precision medicine.

Instead of raising private capital, GTC relies on profits shared with the different members of the co-op. However, Albitar noted that his team welcomes strategic investors who will add and contribute to its growth, "especially if these investors are members of the co-op."

"With this cooperative information, we are sharing the science and medicine, but at the same time, it is democratizing the technology so that other labs — instead of investing a lot of money in a specialized team — are relying on teams that we have centrally at GTC," Albitar said. "At the same time, we are sharing the project with them, and as part of the cooperative concept, we are also sharing profits with sources."

On August 23, 2020 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported that the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Kazia’s paxalisib (formerly GDC-0084) for the treatment of malignant glioma, which includes Diffuse Intrinsic Pontine Glioma (DIPG), a rare and highly aggressive childhood brain cancer (Press release, Kazia Therapeutics, AUG 23, 2020, View Source [SID1234563958]).

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Key Points

Orphan Drug Designation (ODD) is a special status accorded to drugs which are considered promising potential treatments for rare (‘orphan’) diseases, generally defined as those which affect less than 200,000 cases per annum in the United States
ODD can provide drug developers with up to seven years of Orphan Drug Exclusivity (ODE), extending the effective life of a commercial product. It also provides opportunities for grant funding, protocol assistance, and financial benefits, such as a waiver of New Drug Application fees, and tax credits
Receipt of ODD follows award of Rare Pediatric Disease Designation (RPDD) for DIPG on 7 August 2020
Kazia CEO, Dr James Garner, commented, "Taken together, RPDD and ODD provide a powerful suite of incentives, opportunities, and protections for the development of paxalisib in DIPG. We look forward to seeing initial data from the ongoing phase I study in DIPG at St Jude Children’s Research Hospital during the second half of calendar 2020. In parallel, we are working closely with collaborators, advisors, and researchers to determine the best path forward for paxalisib in this devastating disease."

He added, "This award of ODD concludes a program of regulatory optimisation that Kazia has initiated for paxalisib over the past six months. As we orient paxalisib towards commercialization, these special designations from FDA will allow us to move forward in the swiftest and most effective way possible."

Orphan Drug Designation

ODD exists to recognise the development of a drug for a rare disease, which may affect adults or children. ODD provides an additional period of 7.5 years data exclusivity (for a paediatric disease), which allows companies to better defend their products against competition. It also results in a waiver by FDA of fees for a marketing application, under the Prescription Drug User Fees Act (PDUFA fees), which are just under US$ 3 million in FY2020. In addition, drugs with ODD may be eligible for orphan grants by FDA.

Kazia previously received ODD for paxalisib in glioblastoma in February 2018.

Summary of Paxalisib Regulatory Status

Glioblastoma

Most common and most aggressive adult brain cancer

DIPG

Highly aggressive childhood brain cancer

Orphan Designation

February 2018

August 2020

Fast Track Designation

August 2020

Rare Pediatric Disease Designation

n/a

August 2020

Next Steps

Kazia expects to present further data from its ongoing phase II study of paxalisib in glioblastoma at the Society for Neuro-Oncology (SNO) Annual Meeting in November 2020.

Initial efficacy data from the ongoing phase I study of paxalisib in DIPG at St Jude Children’s Research Hospital is expected during 2H CY2020. Precise timing remains uncertain due to pandemic-related disruption in conference schedules, but Kazia expects to provide an update to investors at the earliest opportunity.

Paxalisib has been selected to join the international GBM AGILE pivotal study in glioblastoma, and recruitment is expected to begin in 2H CY2020.

On August 23, 2020 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported that it will hold a conference call on Monday, August 24, 2020 at 8:30 a.m. ET (Press release, Odonate Therapeutics, AUG 23, 2020, View Source [SID1234563953]). To participate in the call, please dial (866) 300-4090 (domestic) or (636) 812-6660 (international) and use conference ID 2881009.

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On August 22, 2020 Novartis reported that the Phase III COMBI-i study evaluating the investigational immunotherapy spartalizumab (PDR001), in combination with the targeted therapies Tafinlar (dabrafenib) and Mekinist (trametinib), did not meet its primary endpoint of investigator-assessed progression-free survival (Press release, Novartis, AUG 22, 2020, View Source [SID1234563952]). The trial was conducted among untreated patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600 mutation-positive cutaneous melanoma, compared to Tafinlar + Mekinist alone3.

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"While the COMBI-i trial did not reach its primary endpoint, the study’s findings give us valuable insights into the role the investigational immunotherapy spartalizumab may play in future cancer therapy combinations and underscore the previously established importance of Tafinlar + Mekinist for these patients," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "Novartis remains committed to melanoma patients through ongoing research, and we continue to deliver the approved combination therapy Tafinlar + Mekinist to patients around the world. We extend our gratitude to the patients and investigators who participated in the COMBI-i study. Their partnership has expanded our understanding of spartalizumab and its potential role in future cancer treatments."

Novartis and the COMBI-i study investigators will continue to review the data to learn more from the results, which are expected to be submitted for presentation at a future medical meeting. Novartis remains committed to exploring new uses for immunotherapy in cancer treatment, including the ongoing development of spartalizumab, across a range of tumor types.

About the COMBI-i Study3
COMBI-i was a randomized, double-blind, placebo-controlled, Phase III study comparing the combination of anti-PD1 spartalizumab with Tafinlar (dabrafenib) and Mekinist (trametinib) versus the combination of placebo with Tafinlar and Mekinist. The study was conducted among previously untreated patients with unresectable or metastatic BRAF V600 mutation-positive melanoma. The COMBI-i study was conducted in three parts. Results reported today are from part 3 of the trial.

About Spartalizumab (PDR001)
Spartalizumab is an investigational monoclonal antibody directed against the human programmed death-1 (PD-1) receptor. Its development program continues investigating the immunotherapy across a range of tumor types.

About Tafinlar + Mekinist Combination
Tafinlar and Mekinist are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

That has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
That has a certain type of abnormal "BRAF" (V600E or V600K mutation-positive) gene
Tafinlar and Mekinist are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal "BRAF" gene from coming back after the cancer has been removed by surgery.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal "BRAF V600E" gene.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

That has spread to other parts of the body and you have no satisfactory treatment options, and
That has a certain type of abnormal "BRAF" gene
Tafinlar, in combination with Mekinist, should not be used to treat people with wild-type BRAF melanoma. Mekinist should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that Tafinlar and Mekinist , in combination, are right for you.

It is not known if Tafinlar and Mekinist are safe and effective in children.

Tafinlar and Mekinist, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When Tafinlar is used in combination with Mekinist, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like "coffee grounds," or red or black stools that look like tar.

Mekinist, alone or in combination with Tafinlar, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider immediately if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

Tafinlar, in combination with Mekinist, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of Tafinlar and Mekinist can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

Tafinlar, in combination with Mekinist, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

Tafinlar, in combination with Mekinist, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with Tafinlar in combination with Mekinist, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of Tafinlar in combination with Mekinist. In some cases, these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with Tafinlar in combination with Mekinist. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.

Tafinlar may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

Tafinlar, in combination with Mekinist, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with Tafinlar and Mekinist and for at least 4 months after the last dose of Tafinlar and Mekinist. For women of reproductive potential, Tafinlar and Mekinist, in combination, may harm your unborn baby. Use effective birth control (contraception) during treatment with Tafinlar and Mekinist in combination, and for 4 months after stopping treatment with Tafinlar and Mekinist. The most common side effects for patients with metastatic melanoma are: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma receiving the combination as adjuvant therapy are: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.