On June 4, 2021 BerGenBio ASA (OSE:BGBIO), BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that end-of-trial data from a Phase I/II study of bemcentinib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, BerGenBio, JUN 4, 2021, View Source [SID1234583870]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Study Design

Phase I of the study was a dose escalation arm designed to confirm the safety and tolerability of bemcentinib in NSCLC patients as both monotherapy and in combination with erlotinib in patients whose disease had previously progressed on erlotinib alone.

Phase II assessed patients in two groups; those whose disease had progressed on an approved EGFR inhibitor, and those who were responding/stable on erlotinib as a first line treatment. Both groups were treated with bemcentinib and erlotinib to evaluate the safety and activity of the combination, while assessing reversal or prevention of resistance to EGFR inhibition.

Conclusions

Data from the study found that Bemcentinib in combination with erlotinib was well tolerated over extended periods of time, with the longest ongoing patients having been dosed for over 46 months.

The combination led to disease stabilisation and durable tumour responses in a proportion of patients who had previously progressed on EGFR targeted therapy and who were negative for the T790M resistance mutation. In patients who were responding to first line treatment with erlotinib, either stable disease or partial response, the addition of bemcentinib led to further deepening of responses and prolonged the duration of responses beyond 30 months in 4 out of the 13 patients evaluated.

At the time of data cut-off, 2 patients are still participating in the study beyond 34 months of treatment. Ongoing patients at the time of study closure, who wish to continue receiving study treatment, will be offered the drug via an expanded access program.

Presenting author Lauren Byers, M.D., associate professor of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, in Houston, said: "We are encouraged by the responses observed both in patients whose disease was progressing on EGFRi alone, as well as patients already in remission with erlotinib. In particular we were pleased to see durable responses exhibited by a number of patients on the study, with two patients continuing to be dosed with bemcentinib beyond 36 months. This is a good indicator that
bemcentinib offers excellent tolerability as well as the potential for anti-tumour activity and we look forward to following their progress as their treatment continues"

Byers reports past advisory board participation for BerGenBio.

Richard Godfrey, CEO of BerGenBio, said: "This end of study data shows the potential of bemcentinib as a combination treatment alongside EGFR inhibitors such as erlotinib and osimertinib, which are established treatments and widely used in indications such as NSCLC in patients with the EGFR driver mutation. We believe that further clinical investigation is needed to fully explore this potential, and look forward to discussing our findings further with our colleagues at ASCO (Free ASCO Whitepaper)."

Details of the presentation, also available on the investor section of BerGenBio’s website, are as follows:

E-poster title: Ph I/II study of oral selective AXL inhibitor bemcentinib (BGB324) in combination with erlotinib in patients with advanced EGFRm NSCLC: end of trial update

Session: Lung Cancer – Non-Small Cell Metastatic

Abstract ID: 9110

Date/Time: Friday, June 4, 2021 at 9:00 AM (EDT)

Authors: Byers et al.

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.

In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the SARS-CoV-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment.

Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response. Data from a Phase II in human clinical trial has shown that treatment with AXL inhibitor bemcentinib increased the rate ventilator free survival in hospitalised COVID-19 patients.

In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.

On June 4, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported two trial in progress posters, on the Phase 1 INNATE clinical trial and the Phase 2 SELECT clinical trial, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting (Press release, Jounce Therapeutics, JUN 4, 2021, View Source [SID1234583507]). INNATE, a proof-of-concept (POC) trial, is evaluating Jounce’s lead macrophage program JTX-8064 (anti-LILRB2/ILT4 inhibitor) as a monotherapy and in combination with pimivalimab (anti-PD-1 inhibitor, formerly known as JTX-4014) in patients with a variety of advanced solid tumors. SELECT, Jounce’s second POC trial, is evaluating pimivalimab as a monotherapy and in combination with vopratelimab (ICOS agonist) in a novel biomarker selection paradigm in PD-(L)1 naïve non-small cell lung cancer patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our INNATE trial is rapidly progressing through dose escalation and we are on-track to begin indication-specific, POC, monotherapy and pimivalimab combination expansion cohorts in the second half of this year," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Furthermore, we are excited to announce the expansion cohort indications for INNATE, which were selected using our translational data-driven approach, linking JTX-8064’s mechanism to tumor types in three groups of patients including: PD-(L)1 inhibitor experienced and resistant, PD-(L)1 inhibitor naïve and historically resistant, and PD-(L)1 inhibitor and historically more sensitive. JTX-8064 is one of only two clinical-stage LILRB2 programs in development and we expect it to be the first program to initiate expansion cohorts in four of our chosen tumor types. We are also pleased to see TISvopra positivity rates tracking with expectations in our biomarker selection trial, SELECT, and we remain on-track to report data next year."

Poster Presentation Details:

Poster Title: Phase 1, First-in-Human trial of JTX-8064, an anti-LILRB2/ILT4 monoclonal antibody, as monotherapy and in combination with anti-PD-1 in adult patients with advanced solid (INNATE)
Presenter: Kyriakos P. Papadopoulos, MD, South Texas Accelerated Research Therapeutics (START), San Antonio, TX
Session Title: Developmental Therapeutics – Immunotherapy
Abstract Number: TPS2672
Date and Time: Friday, June 4, 2021; 9:00am ET
Highlights from the trial in progress poster include the selection criteria for expansion cohorts in the ongoing Phase 1 INNATE trial and an outline the future biomarker plan:

Expansion cohort selection was informed using human histoculture and gene signature analysis from Jounce’s Translational Science Platform and includes PD-(L)1 naïve and experienced patients as well as PD-(L)1 sensitive and resistant tumor types.
The INNATE trial is divided into 4 stages with indication-specific expansion cohorts intended to establish proof-of-concept for JTX-8064:
JTX-8064 monotherapy dose escalation in relapsed / refractory solid tumors
JTX-8064 plus pimivalimab dose escalation in relapsed / refractory solid tumors
JTX-8064 monotherapy expansion in PD-(L)1i naïve platinum resistant ovarian cancer
JTX-8064 plus pimivalimab expansions in:
PD-(L)1i naïve platinum resistant ovarian cancer
PD-(L)1i naïve head and neck squamous cell carcinoma (HNSCC)
PD-(L)1i naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS)
PD-(L)1i experienced non-small cell lung cancer (NSCLC)
PD-(L)1i experienced clear cell renal cell carcinoma (ccRCC)
PD-(L)1i experienced triple negative breast cancer (TNBC)
PD-(L)1i experienced cutaneous squamous cell carcinoma (cSCC).
The dose for expansion cohorts will be selected based on safety, pharmacokinetic and receptor occupancy data from the monotherapy dose escalation stage of INNATE.
Archival and pre-treatment tumor biopsies as well as pre- and post-treatment blood samples will be collected to evaluate a number of potential predictive and pharmacodynamic biomarkers using Jounce’s Translational Science Platform.
Poster Title: Phase 2 Study of PD-1 Inhibitor JTX-4014 (Pimivalimab) Alone and in Combination with Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects with Metastatic NSCLC After One Prior Platinum-containing Regimen (SELECT)
Presenter: Oleh Kobziev, MD, Regional Center of Oncology, Kharkiv, 61070, Ukraine
Session Title: Lung Cancer – Non-Small Cell Metastatic
Abstract Number: TPS9137
Date and Time: Friday, June 4, 2021; 9:00am ET

The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker

TISvopra may serve as a unique biomarker for potential increased benefit for both pimivalimab monotherapy as well as pimivalimab in combination with vopratelimab.
Data from Jounce and a third-party ICOS agonist program support an ICOS-focused biomarker selection strategy to identify patients that may benefit from ICOS agonism.
Early screening data from SELECT support Jounce’s estimate that approximately 20% of PD-(L)1i naïve non-small cell lung cancer patients tested for TISvopra in the study would meet the TISvopra positivity threshold.
SELECT is on-track to report clinical data in 2022.
Both posters will be available on the "Our Pipeline" section of the Jounce Therapeutics website under "Publications" at www.jouncetx.com.

About JTX-8064

JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 and 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899) of JTX-8064 as a monotherapy and in combination with Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014) is currently enrolling patients with advanced solid tumors.

About Pimivalimab

Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. Pimivalimab is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors.

About Vopratelimab

Vopratelimab is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is currently being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with Jounce’s internal investigational PD-1 inhibitor, pimivalimab (formerly JTX-4014), compared to pimivalimab alone. The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor. SELECT is powered to demonstrate the statistical superiority of the combination of vopratelimab plus pimivalimab compared to pimivalimab.

On June 4, 2021 Glycotope GmbH, a biotechnology company developing antibodies against proteins carrying tumor-specific carbohydrate structures, reported it is presenting two posters at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held virtually this year due to COVID-19 (Press release, Glycotope, JUN 4, 2021, View Source [SID1234583526]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Henner Kollenberg, Managing Director of Glycotope GmbH commented: "The data presented at ASCO (Free ASCO Whitepaper) highlight our ability to draw on our long-standing expertise in glyco-biology to generate novel biopharmaceuticals targeting cancer indications. The data showed that a Glycotope-developed anti-TA-MUC1 antibody combined with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors is safe and feasible and exhibited interesting anti-tumour activity."

Poster details are as follows:

Poster 2524

Title: Safety and tolerability results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors
Session: Poster Session: Developmental Therapeutics—Immunotherapy
Abstract ID: 332635

Download: View Source

Poster 2522
Title: Activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors

Session: Poster Session: Developmental Therapeutics—Immunotherapy
Abstract ID: 329709

On June 4, 2021 Notable Labs Inc., a leader in technology-powered life science with a proprietary platform for predicting patient outcomes and accelerating precision drug development, reported top-line results from its clinical response prediction technology platform in a pediatric acute myeloid leukemia (AML) study to be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 4th-8th (Press release, Notable Labs, JUN 4, 2021, View Source [SID1234583542]). The data will be presented by Dr. Alexandra Stevens at Texas Children’s Cancer Center and highlights the correlation of functional drug sensitivity screening using Notable’s predictive technology platform with clinical outcomes of pediatric patients.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the exploratory study, blood or bone marrow samples from 22 de novo pediatric AML patients prior to receiving pre-induction chemotherapy were processed using Notable’s predictive technology platform. Chemosensitivity profiles across a broad spectrum of ex vivo conditions were analyzed and integrated into a predictive measure for individual patients. This measure of ex vivo drug sensitivity correlated with the patients’ clinical results of minimal residual disease and one year relapse-free survival.

"Our collaboration with one of the leading pediatric medical centers further demonstrates the potential of Notable’s prediction technology in identifying and fast-tracking combination therapies in a real-world situation." said Dr. Thomas Bock, CEO of Notable. Dr. Stevens added, "These results are a critical step forward towards our vision of precision medicine where treatments are focused on those patients who will clinically respond, especially for hard-to-treat patient populations."

Details of the presentation are as follows:

Poster Presentation

Title: Ex Vivo Drug Sensitivity Assay Correlates with Clinical Response in Pediatric AML
Session Name: Poster Session: Pediatric Oncology
Abstract Number: 10032
Presentation Time: Available beginning June 4th, 2021

On June 4, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported a clinical trial collaboration with Roche to evaluate SRF388, Surface’s investigational anti-IL-27 antibody, in combination with Roche’s atezolizumab and bevacizumab in patients with treatment-naïve hepatocellular carcinoma (HCC) (Press release, Surface Oncology, JUN 4, 2021, View Source [SID1234583559]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Atezolizumab plus bevacizumab has been shown to significantly improve overall survival and, as reflected in many global clinical practice guidelines, is the new standard of care for unresectable or metastatic HCC. Evolving preclinical and epidemiologic data suggest a significant role for the immunosuppressive cytokine IL-27 in HCC and in resistance to PD-1 pathway blockade. Therefore, the addition of SRF388 to the proven efficacy of the atezolizumab/bevacizumab regimen has the potential to further improve outcomes in this challenging disease.

"At Surface, we are committed to identifying and accelerating the delivery to patients of life-changing treatments, whether as a single agent or in scientifically and clinically appropriate combinations," said Alison O’Neill, M.D., chief medical officer at Surface Oncology. "This collaboration leverages Roche’s deep experience in hepatocellular carcinoma and Surface’s commitment to rationally and rapidly develop SRF388, a first-in-class antibody against IL-27, to provide meaningful benefit to patients with liver cancer."

About SRF388:
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver and kidney cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of hepatocellular carcinoma from the FDA.