On May 29, 2020 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the final results from the GENUINE Phase 3 study evaluating the combination of ublituximab, the Company’s novel glycoengineered anti-CD20 monoclonal antibody, plus ibrutinib compared to ibrutinib alone in patients with previously treated high-risk chronic lymphocytic leukemia (CLL) at the 56thAmerican Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting (Press release, TG Therapeutics, MAY 29, 2020, View Source [SID1234558738]).

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Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "We are extremely pleased with the final results of the GENUINE Phase 3 trial presented today. Not only is this the first randomized trial to show a PFS benefit with the addition of an anti-CD20 antibody to ibrutinib, compared to ibrutinib monotherapy, it was also highly encouraging to see the combination significantly improved overall response rate, complete response rate, and importantly increased the rates of undetectable minimal residual disease." Mr. Weiss continued, "We believe these data support the potential of combination therapies to improve outcomes for patients with high risk CLL, especially those with 17p deletion/TP53 mutation, who continue to progress more rapidly than those without high risk cytogenetics."

Details of the data presentation are included below.

Presentation Title: Effect of Adding Ublituximab to Ibrutinib on PFS, ORR, and MRD Negativity in Previously Treated High-Risk Chronic Lymphocytic Leukemia: Final Results of the GENUINE Phase III Study

The GENUINE trial is an open-label, multicenter, randomized, Phase III study in relapsed or refractory high-risk CLL (del17p, del11q, or TP53mutation). This presentation includes data from 117 patients treated with either ublituximab plus ibrutinib (n=59) or ibrutinib alone (n=58). As of the cut-off date of September 1, 2019, patients had a median follow-up time of 41.9 months. The primary endpoint for this trial was overall response rate (ORR) as determined by an independent review committee (IRC). The secondary endpoints included progression free survival (PFS) and complete response (CR) rate as determined by an IRC, and undetectable minimal residual disease (uMRD) assessed by central lab.

Efficacy and safety highlights include:

The addition of ublituximab to ibrutinib compared to ibrutinib monotherapy significantly improved ORR (93% compared to 78%; p=0.019), complete response/complete response with incomplete blood count recovery (CR/CRi) rate (20% vs. 5%; p=0.024), and increased rates of uMRD (46% vs. 7%; p<0.001) in patients with relapsed/refractory CLL with high-risk cytogenetics
At a median follow-up of 41.9 months, median PFS was not reached in the ublituximab plus ibrutinib arm and was 35.9 months in the ibrutinib monotherapy arm (hazard ratio 0.46), with del17p/TP53mut patients seeing the greatest difference in PFS
The addition of ublituximab to ibrutinib did not significantly alter the known safety profile of ibrutinib however the combination resulted in slightly higher rates of neutropenia (36% compared to 21%) and atrial fibrillation (14% compared to 7%)
The data presented is available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

ABOUT THE GENUINE PHASE 3 STUDY
The GENUINE Phase 3 study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of ublituximab plus ibrutinib compared to ibrutinib alone in adult patients with high-risk chronic lymphocytic leukemia (CLL) who received at least one prior therapy for their disease.

Patients received ibrutinib orally at 420 mg once daily in both arms and in the combination arm those patients also received intravenous infusions of ublituximab at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the combination arm who had not progressed received quarterly infusions of ublituximab maintenance at 900 mg.

On May 29, 2020 Caris Life Sciences, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, reported that it will present results from a study today that characterize KRAS mutations in patients with non-small cell lung cancer (NSCLC) (Press release, Caris Life Sciences, MAY 29, 2020, View Source [SID1234558771]). In this study, the molecular profiles of more than 17,000 patients with NSCLC were evaluated using the Caris Molecular Intelligence platform, which were then classified based on specific types of KRAS mutations using a 592-gene DNA sequencing panel. The study found that KRAS mutations are relatively common in NSCLC and that differences between KRAS mutation subtypes warrant further investigation in how they could guide treatment decisions, including the use of targeted and immuno-oncology drugs.

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Across 17,113 NSCLC patients, KRAS mutations were present in 27% of samples (n=4,706), with KRAS G12C being the most common variant and present in 40% of samples that exhibited a mutation. KRAS G12C was associated with the highest rate of PD-L1 expression. The rate of high tumor mutational burden (TMB) (>10 mutations/MB) was significantly different across KRAS mutation subtypes and was most frequently seen in KRAS G13X (68.3%) and least frequently in G12D (43.2%). KRAS mutations were more commonly seen in adenocarcinoma versus squamous subtype (37.2% vs. 4.4%)

The full results will be presented today during a poster session (Abstract 9544/Poster 310) as part of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO20) Virtual Scientific Program. The poster is titled, "Characterization of KRAS mutations (mt) in non-small cell lung cancer (NSCLC)."

In a second study, the molecular profiles of a large cohort of KRAS wild-type (WT) pancreatic tumors were evaluated using DNA sequencing and whole transcriptome sequencing (WTS), which were then classified based on specific types of KRAS mutations using a 592-gene DNA sequencing panel. The study looked to assess the prevalence of alterations that could represent targets for personalized treatment. Researchers found that the use of WTS, in combination with DNA sequencing, identified activated molecular pathways in the majority of KRAS WT tumors, and that these tumors are significantly more enriched with targetable alterations (e.g., BRAF, ALK, ROS1, NRG1, MSI-H) compared to KRAS mutant tumors. These findings suggest a potential benefit of using targeted therapies to treat patients with KRAS WT tumors.

"While KRAS mutations in pancreatic cancer are found in the majority of cases, we used comprehensive molecular profiling to generate crucial information on mutations and transcriptional programs found in KRAS wild-type pancreatic cancer that provide additional opportunities for therapeutic intervention in this cancer type that has a low survival rate and few treatment options," said Philip A. Philip, M.D., Ph.D., FRCP., lead investigator of the study and an oncologist with Barbara Ann Karmanos Cancer Institute at Wayne State University, a member of the Caris Precision Oncology Alliance.

The full results will be presented today during a poster session (Abstract 4629/Poster 237). The poster is titled, "Alterations in targetable molecular pathways are enriched in KRAS wild-type (WT) pancreatic cancer (PC)."

"Our data at ASCO (Free ASCO Whitepaper)20 continue to reinforce the power of molecular profiling and precision medicine technologies in changing the face of cancer treatment," said W. Michael Korn, M.D., Chief Medical Officer at Caris Life Sciences. "The combination of Next-Generation DNA Sequencing and whole transcriptome sequencing is giving clinicians new insights and clearer direction in how they approach non-small cell lung cancer and pancreatic cancer, two particularly difficult-to-treat cancers."

Additional Presentations Provide Key Insight Into The Genetic Profile of Cancer
Caris will present additional data from studies highlighting the distinct molecular landscapes of patients across several cancer types, including mesothelioma and gastroesophageal cancers. Better understanding of a tumor’s genomic landscape and distribution of immune biomarkers has the potential to enable the development of new, novel therapies and can help physicians prescribe the optimal treatment to each patient.

A study, "Genomic Landscape and Immune Phenotype of Malignant Pleural Mesothelioma" (Abstract 9056/Poster 249), found that the majority of mesothelioma tumors harbor at least one alteration in key cellular pathways, with homologous recombination (HR) pathway mutations the most common.
"Molecular correlates of PD-L1 expression in patients (pts) with gastroesophageal (GE) cancers" (Abstract 4558/Poster 166) is the largest study to investigate the distinct molecular landscape of patients with different PD-L1 expression levels in GE cancers. These data can be used by oncologists to bring the right treatment to the right patient and by researchers to develop new combination immunotherapy regiments in GE cancers.
"As we continue to learn more about the molecular landscape of cancer, it is important to study all cancers, including those that are more uncommon and those that have an established treatment paradigm," said Chadi Nabhan, M.D., MBA, FACP, Chairman of the Caris Precision Oncology Alliance. "At Caris, our goal is to work with leading institutions to bring precision medicine to all people living with a cancer diagnosis, so that each patient can receive the best possible therapy for their own distinct cancer."

About the Caris Precision Oncology Alliance
A collaborative and growing network of leading cancer centers that demonstrate a commitment to precision medicine. The Alliance currently comprises 38 academic, hospital and community-based cancer institutions, including 12 NCI-designated Comprehensive Cancer Centers and now includes over 2,200 physicians, spanning more than 440 locations, who provide services for over 350,000 people with cancer each year.

On May 29, 2020 BridgeBio Pharma, Inc. (Nasdaq: BBIO) affiliate QED Therapeutics reported that it will present data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program showing clinical advancement for infigratinib, QED’s oral FGFR1-3 inhibitor, in both urothelial carcinoma and cholangiocarcinoma (CCA) (Press release, BridgeBio, MAY 29, 2020, View Source [SID1234576229]).

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Title: Infigratinib (BGJ398) in advanced/unresectable or metastatic urothelial carcinoma demonstrates consistent treatment response in both first-line and later-line treatment settings

Abstract: 5038

Presenter: Yung Lyou, City of Hope Comprehensive Cancer Center

An analysis of response rates in patients with advanced/unresectable or metastatic urothelial carcinoma based on the amount of prior lines of treatment showed consistent response to infigratinib. The objective response rate (ORR) for all patients (n=67) was 25% (95% CI 15.5-37.5), while the ORR for patients receiving infigratinib as first-line treatment (n=13) saw a response rate of 31% (95% CI 9.1-61.4) compared to 24% (95% CI 13.5-37.6) for patients receiving infigratinib as a second-line or later treatment (n=54). All eight patients in the study with upper tract urothelial carcinoma (UTUC) received infigratinib as second-line or later therapy. The response rates were higher for patients with UTUC, with an ORR of 50% (95% CI 15.7–84.3) and a disease control rate of 100%. In the study, treatment emergent adverse events occurring in >30% of patients were: hyperphosphatemia (46%), elevated creatinine (42%), fatigue (37%), constipation (37%), anemia (36%), decreased appetite (33%), dry mouth (31%), and alopecia (31%).

"These findings support the design of the ongoing, placebo-controlled PROOF 302 study to evaluate the efficacy of infigratinib in adjuvant urothelial carcinoma," said author and PROOF 302 trial lead Sumanta Pal, MD, professor of medical oncology and therapeutics research at City of Hope Comprehensive Cancer Center. "The results in upper tract urothelial cancer (UTUC) build upon earlier research that the disease has a different genetic profile than urothelial carcinoma of the bladder, particularly with respect to FGFR3 alterations, and warrants further investigation in an even earlier setting."

Title: A retrospective analysis of post second-line chemotherapy treatment outcomes for patients with advanced or metastatic cholangiocarcinoma and FGFR2 fusions

Abstract: 4591

Presenter: Milind M. Javle, MD Anderson Cancer Center

In a retrospective analysis of a subset of a single-arm Phase 2 study of infigratinib (n=37), outcomes from patients with FGFR-fusion-positive bile duct cancer receiving infigratinib as third- and later-line therapy were compared with the tumor response when those same patients received second-line therapy with chemotherapy. Treatment with infigratinib resulted in progression free survival (PFS) improvements. The median PFS was 6.8 months (95% CI 3.9-7.8 months) for third- and later-line infigratinib treatment compared to 4.6 months (95% CI 2.7-7.2 months) for second-line chemotherapy.

"Through this retrospective analysis, we can see that infigratinib may have potential for patients whose tumors progress after second-line chemotherapy," said Susan Moran, MD, MSCE, chief medical officer for QED. "These data support continued investigation of infigratinib in patients with FGFR-driven cholangiocarcinoma."

On May 29, 2020 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained an approval from the Ministry of Health, Labour and Welfare (MHLW) for expanded use of the genomic mutation analysis program, FoundationOne CDx Cancer Genomic Profile as a companion diagnostic of the Novartis’ investigational MET inhibitor, capmatinib (INC280) for the treatment of unresectable advanced and/or metastatic non-small cell lung cancer (NSCLC) with that leads to MET exon 14 skipping (METex14) (Press release, Chugai, MAY 29, 2020, View Source [SID1234558655]).

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"We are pleased that FoundationOne CDx Cancer Genomic Profile was approved as a companion diagnostic of an investigational MET inhibitor, capmatinib. Since the standard treatment of NSCLC is decided based on whether the cancer has a driver mutation, we believe NSCLC is one of the cancer types that comprehensive genomic profiling can particularly contribute to its treatment decision," said, Dr. Osamu Okuda, Chugai’s President and COO. "By continuing to collaborate with many biopharma partners, we will expand the companion diagnostic functions and are committed to working toward the realization of precision medicine."

The approval aims to expand the program for use as a companion diagnostic to aid in identifying patients who could benefit from capmatinib for the treatment of unresectable advanced and/or metastatic NSCLC with METex14 by detecting mutations that lead to METex14. It is estimated that 3-4% of all patients with NSCLC have an identified METex141) and is said to be a poor prognosis factor2). Capmatinib is a selective MET inhibitor and is confirmed to strongly inhibit the kinase activity of the METex143). Efficacy and safety of capmatinib are investigated in patients with advanced and/or metastatic NSCLC in the phase II GEOMETRY mono-1 study conducted by Novartis. Novartis Japan K.K. has submitted the regulatory application of capmatinib to the MHLW.

Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. The program is available as a companion diagnostic for multiple molecular-targeted drugs approved in Japan.

As a leading company in the field of oncology, Chugai is committed to realize advanced personalized oncology care and contribute to patients and healthcare professionals through improving access to comprehensive genomic profiling.

Approval information The underlined part has been newly added.
Intended uses or indications

The Product is used for comprehensive genomic profiling of tumor tissues in patients with solid cancers.
The Product is used for detecting gene mutations and other alterations to support the assessment of drug indications listed in the table below.
Alterations Cancer type Relevant drugs
EGFR exon 19 deletions and EGFR exon 21 L858R alterations Non-small cell lung cancer (NSCLC) afatinib dimaleate, erlotinib hydrochloride, gefitinib, osimertinib mesylate
EGFR exon 20 T790M alterations osimertinib mesylate
ALK fusion genes alectinib hydrochloride, crizotinib, ceritinib
ROS1 fusion genes entrectinib
MET exon 14 skipping alterations capmatinib hydrochloride hydrate
BRAF V600E and V600K alterations Malignant melanoma dabrafenib mesylate, trametinib dimethyl sulfoxide, vemurafenib
ERBB2 copy number alterations (HER2 gene amplification positive) Breast cancer trastuzumab (genetical recombination)
KRAS/NRAS wild-type Colorectal cancer cetuximab (genetical recombination), panitumumab (genetical recombination)
NTRK1/2/3 fusion gene Solid tumors entrectinib
BRCA1/2 alterations Ovarian cancer olaparib
Trademarks used or mentioned in this release are protected by laws.

Reference

Salgia R. MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale. Mol Cancer Ther. 2017; 16(4):555-565.
Tong JH, Yeung SF, Chan AWH, et al. MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non–Small Cell Lung Carcinoma with Poor Prognosis. Clin Cancer Res. 2016; 22(12):3048-3056.
Fujino T, Kobayashi Y, Suda K, et al. Sensitivity and Resistance of MET Exon 14 Mutations in Lung Cancer to Eight MET Tyrosine Kinase Inhibitors In Vitro. J Thorac Oncol: 2019 Oct;14(10):1753-1765

On May 29, 2020 Alligator Bioscience (Nasdaq Stockholm: ATORX), reported that the company today presents additional novel data from the ongoing Phase I clinical trial with the bispecific drug candidate ATOR-1015 developed as tumor-directed therapy for metastatic cancer, which further validates the potential of the drug (Press release, Alligator Bioscience, MAY 29, 2020, View Source [SID1234558672]). The presentation will be held at the ASCO (Free ASCO Whitepaper) (American Society of Clinical Oncology) Annual Meeting, which this year is being held virtually.

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The results from the evaluation of doses up and including 600 mg (about 10 mg/kg) show that ATOR-1015 is well tolerated, and dose-escalation has continued to 750 mg (12.5 mg/kg). In this presentation, 21 patients with varying cancer types (colon cancer, eye melanoma, pancreatic cancer, ovarian cancer, gallbladder cancer, gastric cancer, and melanoma) are included and evaluated in terms of safety. The drug related adverse events in the study have generally been mild and transient. No dose-limiting toxicity or severe immune-related adverse events have been reported.

"The results presented at ASCO (Free ASCO Whitepaper) truly support the fact that ATOR-1015 could be a safer and more efficacious drug than current treatment options for spread cancer disease. We are consequently very much looking forward to moving ATOR-1015 into efficacy studies," said Per Norlén, CEO of Alligator Bioscience.

Due to the positive tolerability profile of ATOR-1015, dose escalation will continue at even higher doses than expected but still allows for a preliminary efficacy readout in melanoma patients already towards the end of 2021.

The ASCO (Free ASCO Whitepaper) poster presentation with the title "A first-in-human phase I study in patients with advanced and/or refractory solid malignancies to evaluate the safety of ATOR-1015, a CTLA-4 x OX40 bispecific antibody" is available on the company website View Source

For further information, please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Phone +46 46 540 82 06
E-mail: [email protected]

This information is such information as Alligator Bioscience AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 2:00 p.m. CEST on May 29, 2020.

About the ATOR-1015 Phase I study
The Phase I study with ATOR-1015 is a dose escalation study in patients with metastatic cancer (NCT03782467). The primary endpoint of the study is to investigate the safety and tolerability of ATOR-1015 and to determine the recommended dose for subsequent Phase II studies. The first patient was dosed in March 2019 and following the establishment of the maximum tolerable dose or recommended dose for Phase II, further clinical development of ATOR-1015 is planned, primarily for the treatment of malignant melanoma.

About ATOR-1015
ATOR-1015, wholly owned by Alligator, is a bispecific CTLA-4 antibody developed as tumor targeted immunotherapy with increased capacity for killing regulatory T cells. ATOR-1015 binds to two different immune receptors – the checkpoint receptor CTLA-4 and the co-stimulatory receptor OX40. The immune activation is increased in areas where both target molecules are expressed at high levels, notably in the tumor microenvironment, which can lead to reduced side effects.