January 2021 – Page 87 – 1stOncology™: Cancer Intelligence Service

GT Biopharma Announces Eighth Patient Begins Treatment Of GTB-3550

On January 12, 2021 GT Biopharma, Inc. (OTCQB: GTBP) (GTBP.PA) an immuno-oncology company focused on innovative therapies based on the Company’s proprietary NK cell engager (TriKE) technology platform reported the continuation of enrollment with patient 8 in its GTB-3550 clinical trial following the conclusion of a 30-day Covid-19 related pause in enrolling patients in all clinical trials currently being conducted at the University of Minnesota’s Masonic Cancer Center (Press release, GT Biopharma, JAN 12, 2021, View Source [SID1234573930]).

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Patients with CD33+ malignancies (primary induction failure or relapsed AML with failure of one reinduction attempt or high-risk MDS progressed on two lines of therapy) age 18 and older are eligible to participate in the GTB-3550 TriKE clinical trial (NCT03214666). The primary endpoint of the Study is to identify the maximum tolerated dose (MTD) of GTB-3550 TriKE. Correlative objectives include the number, phenotype, activation status and function of NK cells and T cells.

GTB-3550 TriKE Demonstrates Clinical Benefit in Patients and 61.7% Reduction in Cancer Burden in patient 7

The GTB-3550 TriKE clinical trial commenced patient enrollment in February 2020 for the treatment of relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS). To date, seven patients have been enrolled in the clinical trial; two patients treated at 5 mcg/kg/day, two patients treated at 10 mcg/kg/day, two patients at 25 mcg/kg/day, and one patient treated at 50 mcg/kg/day. All seven patients have completed therapy. The results to date have been positive and the company continues to expand the enrollment.

Clinical Benefit Achieved and Reduction in Cancer Burden in HR-MDS Patient

A high-risk myelodysplastic syndromes (HR-MDS) patient had failed hypomethylating agent and Luspatercept therapies prior to being treated with GTB-3550 at 50mcg/kg/day (three consecutive 96-hour continuous infusions). The patient achieved bone marrow blast level reduction from 12% before GTB-3550 therapy to 4.6% post GTB-3550 therapy determined by morphological assessment (61.7% reduction in cancer cells), and had stable hematologic parameters including normal platelet counts throughout therapy. Following this single course of GTB-3550 therapy and the significant reduction in bone marrow blast levels, the patient demonstrated clinical benefit from GTB-3550 therapy, and qualified for and has received a hematopoietic stem cell transplant (HSCT). The only treatment with curative intent for a majority of elderly HR-MDS or relapsed/refractory AML patients is allogeneic hematopoietic stem cell transplant (HSCT). GTB-3550 TriKE therapy represents a novel, low intensity therapeutic option which has the potential to increase HSCT eligibility for elderly HR-MDS and relapsed/refractory AML patients.

Achievement of Stable Disease and Reduction in Cancer Burden in AML Patients

Two patients with relapsed/refractory acute myeloid leukemia who has previously failed prior therapies prior to being treated with GTB-3550; one patient treated at 5mcg/kg/day achieved stable disease and another patient treated at 25mcg/kg/day experienced a 33% reduction in bone marrow blast levels.

No Toxicities / Potent Native NK Cell Activation and Proliferation without Supplemental NK Cell Therapy

No signs of clinical immune activation, and no dose limiting toxicity such as cytokine release syndrome (CRS) or serious adverse events (SAEs) or fevers, tachycardia or constitutional symptoms have been observed in any patient treated to date with GTB-3550 TriKE. Correlative studies also showed no shedding of CD16 from patient’s NK cells, and potent NK cell activation, proliferation and target cell killing without the need for supplemental autologous NK cell therapy.

Targeted delivery of IL-15 to NK cells via GTB-3550 TriKE therapy showed preferential proliferation of NK cells, significantly less effect on CD8+ T-cells, and no observed toxicity at 25x the previous reported MTD for continuous infusion of recombinant human IL-15. GTB-3550 TriKE is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies,

Mr. Anthony Cataldo, Chairman and Chief Executive Officer of GT Biopharma commented "We are pleased to once again be allowed to proceed with patient enrollment now that the Covid-19 enrollment pause has been removed at the University of Minnesota’s Masonic Cancer Center."

About GTB-3550 TriKE

GTB-3550 is the Company’s first TriKE product candidate being initially developed for the treatment or relapsed/refractory acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (HR-MDS). GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. The natural killer (NK) cell stimulating cytokine human IL-15 portion of the molecule provides a self-sustaining signal that activates NK cells and enhances their ability to kill cancer cells.

New Prospective Data Demonstrate Low False-Positive Rate for Screening Average-Risk People Age 45-49 for Colorectal Cancer with Cologuard®

On January 12, 2021 Exact Sciences Corp. (Nasdaq: EXAS) reported that data published today in Cancer Prevention Research, a Journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), that expands on foundational clinical study findings to include a key younger population (Press release, Exact Sciences, JAN 12, 2021, View Source [SID1234573929]). Study results show that among average-risk adults between the ages of 45 and 49 Cologuard (mt-sDNA) demonstrated test specificity of 95.2% in participants with non-advanced precancerous lesions or negative findings at colonoscopy and 96.3% in only those with negative colonoscopy findings. These analyses support potential risk mitigation and cost prevention due to unnecessary diagnostic procedures when using Cologuard as a colorectal cancer screening tool in this younger population.

Cologuard is a U.S. Food & Drug Administration (FDA)-approved, non-invasive stool DNA test for colorectal cancer for average-risk people. In September 2019, the FDA approved Cologuard for average-risk individuals beginning at age 45, expanding the Cologuard label to include this critical younger adult population.

Study is among the first to evaluate the use of a colorectal cancer screening method in patients between ages of 45-49.

"These new data support the critical role an effective, non-invasive option like Cologuard plays in screening people ages 45 to 49," said Kevin Conroy, chairman and CEO of Exact Sciences. "Cologuard may appeal to this younger screening population because they can collect sample at home, without missing work or undergoing bowel prep and anesthesia, and only those patients with a positive Cologuard will require a diagnostic colonoscopy."

In a previously published, large clinical study of nearly 10,000 patients 50 and older, Cologuard found 92% of colorectal cancers, including 94% in stages I and II. Specificity for this over 50 population was 87%.

Colorectal cancer is the second leading cause of cancer death for men and women in the United States, in part because many cancers go undetected until later stages when treatment is less effective. Colorectal cancer can be prevented or detected early through screening; however, approximately 44 million Americans remain unscreened, including an estimated 19 million between ages 45 and 49.

The incidence of colorectal cancer in people under the age of 50 has dramatically increased in the last 20 years. Between 2004 and 2015, health care providers diagnosed more than 130,000 cases of colorectal cancer in Americans under age 50. More than half of these cases were diagnosed at an advanced stage, stage III or stage IV, when survival rates are low.

"This study is among the first to evaluate the use of a colorectal cancer screening method in patients between the ages of 45 and 49," said Paul Limburg, M.D., Chief Medical Officer, Screening at Exact Sciences. "The American Cancer Society guidelines and the 2020 draft United States Preventive Services Task Force (USPSTF) guidelines now say that screening should begin at 45, and these data support the use of Cologuard as a first line screening option."

The prospective study included 816 evaluable participants who all completed a Cologuard test and underwent a colonoscopy. Participants were enrolled at 31 sites in the United States from November 2018 through June 2019. They completed Cologuard, followed by a screening colonoscopy within approximately 60 days of enrollment. Participants collected their sample for the Cologuard test prior to doing any bowel preparation necessary for the colonoscopy. All colonoscopies were performed blinded to the Cologuard results.

Specificity was the primary outcome and was measured in participants without colorectal cancer or advanced precancerous lesions and in the subgroup of participants with negative colonoscopic findings. None of the study participants had colorectal cancer, 49 had advanced precancerous lesions, 253 had non-advanced adenomas and 514 had negative colonoscopies. Specificity did not differ between men and women.

Bausch Health Provides Preliminary Update On Fourth-Quarter And Full-Year 2020 Financial Results And Business Recovery

On January 12, 2021 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health" or the "Company") reported that it will provide a preliminary update on its fourth-quarter and full-year 2020 financial results and the continued pace of its business recovery from the COVID-19 pandemic tomorrow, Jan. 13, 2021, during a fireside chat at 10 a.m. ET at the 39th Annual J.P. Morgan Healthcare Conference (Press release, Bausch Health, JAN 12, 2021, View Source [SID1234573927]).

Bausch Health expects its revenue in the fourth quarter of 2020 will be greater than $2.20 billion. For the full year of 2020, the Company anticipates it will outperform the high end of its latest revenue guidance range of $7.80 – $8.00 billion.1

"Bausch Health’s preliminary fourth-quarter and full-year 2020 financial results demonstrate that our Company is continuing its business recovery from the effects of the COVID-19 pandemic driven by strong execution across our businesses. For the full year of 2020, we anticipate our revenue will outperform the high end of our latest revenue guidance range, and we also expect a strong finish to the year with regard to Adjusted EBITDA (non-GAAP)," said Joseph C. Papa, chairman and CEO, Bausch Health. "We look forward to releasing our full financial results for the fourth quarter and full year of 2020 next month."

Additionally, due to strong cash flow in the fourth quarter of 2020, Bausch Health expects to exceed $1 billion in cash generated from operations for the full year of 2020. In total, the Company repaid approximately $900 million of debt in 2020 from cash generated from operations and more efficient cash management, and has no debt maturities or mandatory amortization payments until 2024.

Bausch Health Will Publish Company Update Presentation on Jan. 13, 2021 at 7:00 a.m. ET
Bausch Health will publish a brief company update presentation tomorrow, Jan. 13, 2021, at 7 a.m. ET, that is designed to complement the remarks provided by management at the 39th Annual J.P. Morgan Healthcare Conference. The presentation will provide an overview of the Company’s recent performance and offer insight into future catalysts for 2021 and beyond.

The presentation will be available on the Investor Relations page of the Bausch Health Companies Inc. website at: View Source A live webcast and audio archive of the fireside chat will also be available on the Investor Relations page of the Company’s website.

Janssen to Highlight Commitment to Lung Cancer Science and Innovation with Eight Data Presentations at the International Association for the Study of Lung Cancer’s 2020 World Conference on Lung Cancer

On January 12, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that eight company-sponsored presentations, including two oral presentations, will be featured at the International Association for the Study of Lung Cancer’s (IASLC) 2020 World Conference on Lung Cancer (WCLC) Singapore taking place virtually January 28-31, 2021 (Press release, Johnson & Johnson, JAN 12, 2021, https://www.prnewswire.com/news-releases/janssen-to-highlight-commitment-to-lung-cancer-science-and-innovation-with-eight-data-presentations-at-the-international-association-for-the-study-of-lung-cancers-2020-world-conference-on-lung-cancer-301207007.html [SID1234573926]). The presentations include updated data from the Phase 1 CHRYSALIS study (NCT02609776) evaluating amivantamab in patients with NSCLC and EGFR exon 20 insertion mutations and two studies that characterize the high unmet need and lack of standard of care in patients with exon 20 insertion mutations and the underdiagnosis of these patients in real-world settings.

Amivantamab is an investigational, fully human bispecific antibody that targets tumors by directing immune cell activity against tumors with activating and resistance EGFR mutations and mesenchymal epithelial transition factor (MET) mutations and amplifications.1,2,3,4 Janssen has filed regulatory submissions in the U.S. and Europe seeking approval of amivantamab for the treatment of patients with NSCLC and EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.5 These applications mark the first-ever regulatory submissions of a treatment for patients with NSCLC and EGFR exon 20 insertion mutations.6

"We see an important opportunity to improve the diagnosis and treatment of patients with EGFR-mutated non-small cell lung cancer, especially for individuals with exon 20 insertion mutations. To that end, we look forward to presenting data highlighting the potential of amivantamab in this patient population, and the importance of genetic testing to identify mutations that may impact treatment outcomes," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "We are focused and committed to transforming the trajectory of lung cancer through improved diagnostics, novel therapeutics and interception strategies."

Lung cancer is one of the most common cancers and is the leading cause of cancer deaths worldwide, with NSCLC making up 80 to 85 percent of all lung cancers.7,8 Patients with EGFR exon 20 insertion mutations have a median survival of less than 17 months9, which is much shorter than patients with EGFR exon 19 deletions or L858R mutations, who have a median survival of 32-39 months on current therapies.10

Amivantamab Phase 1 CHRYSALIS Study Shows Promise for Patients with NSCLC and EGFR Exon 20 Insertion Mutations
New data from the Phase 1 CHRYSALIS study evaluating the safety and efficacy of amivantamab in patients with metastatic NSCLC and EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy will be presented as an oral presentation (Abstract #3031). Early results from the CHRYSALIS study were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program (Abstract #9512).11

Mini-Oral Presentation Underscores Unmet Need of Patients with EGFR Exon 20 Insertion Mutations
A mini-oral presentation based on real-world data will provide new insights into the differences in prognoses for patients with NSCLC and EGFR exon 20 insertion mutations compared to those with other EGFR mutations (Abstract #3390).

Real-World Datasets Spotlight Underdiagnosis for Patients with Lung Cancer with Genetic Alterations
Accurate identification of driver mutations is an important part of lung cancer diagnostic and staging processes.12 A new analysis of real-world genomic data that will be presented at the meeting (Abstract #3399) estimates that genetic tests using polymerase chain reaction (PCR) may miss up to 50 percent of tumors with EGFR exon 20 insertion mutations, suggesting significant underdiagnosis exists.

Further details about these data and the science that Janssen is advancing for patients with lung cancer will be made available throughout the IASLC 2020 WCLC via the Janssen Oncology Virtual Newsroom.

Company-sponsored abstracts to be presented at the meeting include:

Abstract No.

Title

Date/Time

Oral Presentation

Abstract #3031

Amivantamab, an EGFR-MET Bispecific Antibody, in EGFR Exon 20 Insertion Mutant Non-Small Cell Lung Cancer

Thursday, January 28th

10:55 pm – 11:05 pm EST / Friday, January 29th 11:55 am – 12:05 pm Singapore Standard Time (SST)

Mini-Oral Presentation

Abstract #3390

Comparative Clinical Outcomes for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutations and Common EGFR Mutations

Friday, January 29th

4:20 am – 4:25 am EST / Friday, January 29th 5:20 pm – 5:25 pm SST

Featured Poster

Abstract #3399

Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-Based Real-World Datasets