1stOncology™: Cancer Intelligence Service – Page 14013 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

BerGenBio extends Phase II trial with bemcentinib and KEYTRUDA® in NSCLC to include patients with disease progression on immune checkpoint inhibitor therapy

On April 2, 2019 BerGenBio ASA (OSE: BGBIO) reported that the first patient has been dosed in an additional cohort ("Cohort B") of an ongoing phase II open-label study of BerGenBio’s selective AXL inhibitor bemcentinib in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in previously treated patients with advanced adenocarcinoma of the lung (NSCLC) (Press release, BerGenBio, APR 2, 2019, View Source [SID1234534951]).

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!

The additional cohort of the BGBC008 trial, being run in collaboration with Merck (known as MSD outside the US and Canada), will extend eligibility to include patients with previously treated advanced NSCLC whose disease is progressing on immunotherapy.

Patients eligible to participate in Cohort B must have disease progression whilst on a therapy regimen which includes an anti-PD(L)1 inhibitor. The trial follows a two-stage design with the opportunity for an early stop for futility and will evaluate the combination’s objective response rate as a primary endpoint. Comprehensive exploratory studies will evaluate biomarkers in tumour and blood indicative of AXL and PD-L1 expression as well as immune modulation.

Preliminary results from Cohort B are expected in H2 2019. BerGenBio is responsible for conducting the trial. Merck will supply KEYTRUDA for use in the study under a collaboration agreement signed in March 2017.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Throughout 2018, we reported encouraging updates from our ongoing proof-of-concept Phase II clinical trial assessing bemcentinib in combination with KEYTRUDA in advanced lung cancer patients post chemotherapy. Patients with AXL positive disease showed particularly good response rates, supporting our belief that selectively inhibiting AXL may act synergistically with immune checkpoint inhibitors in immunotherapy naïve patients. Pre-clinical and translational data strongly suggest that AXL is implicated in anti-PD(L)-1 (checkpoint-inhibitor) therapy failure which has become a large unmet medical need following the rapid uptake of checkpoint inhibitors in first-line lung cancer therapy. Therefore, I am pleased that we are now extending the ongoing trial to test our hypothesis also in patients showing disease progression on checkpoint inhibitors and I look forward to providing updates on both cohorts during 2019."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

END

About NSCLC
It is estimated that more than 230,000 new cases of lung cancer have been diagnosed in the US in 2018 and it is the leading cause of cancer deaths. 65% of NSCLCs are of adenocarcinoma pathology. Although various treatments exist for NSCLC, they are often curtailed by acquired resistance to therapy and immune evasion. Novel treatments overcoming these mechanisms in NSCLC are urgently required.

About the BGBC008 trial
The BGBC008 trial is a Phase II open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated patients with advanced adenocarcinoma of the lung run at centres in the US, UK, Spain and Norway. The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

Patients eligible for participation in Cohort A must have progressed on or after prior therapy excluding immunotherapy whereas patients in Cohort B will be actively progressing on a therapy regimen containing an anti-PD(L)-1 therapy.

Both cohorts follow a two-stage design, Cohort A has previously successfully progressed into the second stage after meeting its first efficacy endpoint. Cohort B will evaluate advancement into stage 2 after 13 patients have been assessed for response.

For more information please access trial NCT03184571 at www.clinicaltrials.gov.

About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms that drive aggressive and life-threatening diseases. In cancer, AXL drives tumour survival, treatment resistance and spread, as well as suppressing the body’s immune response to tumours. AXL expression has been established as a negative prognostic factor in many cancers. AXL inhibitors, therefore, have potential value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities.

Combination of first-in-class NBTXR3, radiotherapy, and anti-PD-1 immunotherapy
demonstrate efficacy in treating resistant pre-clinical in vivo models of lung cancer

On April 2, 2019 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205 – the ‘‘Company’’) a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported preclinical data from studies currently being conducted under its collaborations with The University of Texas MD Anderson Cancer Center and the Weill Cornell Medical College (Press release, Nanobiotix, APR 2, 2019, View Source [SID1234534950]). These results were presented during two poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, currently taking place in Atlanta, Georgia, USA from March 29 to April 3, 2019.

This initial pre-clinical set of NBTXR3/radiotherapy/IO combination data provides further insights into the immuneactivation caused by NBTXR3 and strengthens the understanding of the potential systemic effects provided by NBTXR3. Thus, the Company believes it formulates sound rationale to support its clinical development program investigating the combination of NBTXR3, radiotherapy and IO agents.

Enhancement of anti-PD-1 and anti-CTLA4 efficacy by NBTXR3 nanoparticles exposed to radiotherapy Poster #3225 Yun Hu1, Ping Zhang2, Audrey Darmon2, Maria Angelica Cortez1, Sébastien Paris2, James Welsh1 1MD Anderson Cancer Center, Houston, TX; 2Nanobiotix, Paris, France

In both 344SQ_P (sensitive to anti-PD-1 treatment) and 344SQ_R (resistant to anti-PD-1 treatment) lung cancer models, the combination of anti-PD-1 + radiotherapy + NBTXR3 demonstrated both better control of the treated tumor and the distant untreated tumor as well as increased survival when compared to monotherapy. Importantly, it was observed that this combination decreased spontaneous lung metastasis formation in the anti-PD-1 sensitive 344SQ_P model.

For the CT26.WT colon carcinoma model, as previously reported, NBTXR3 activated by radiotherapy generated an abscopal effect. It was observed that administration of anti-CTLA4 monotherapy demonstrated control of both treated and distant untreated tumors, potentially indicating that the CT26.WT was sensitive to a checkpoint inhibitor. The addition of radiotherapy to anti-CTLA4 only improved the tumor control modestly compared to antiCTLA4 alone. In contrast, the combination of anti-CTLA4 + radiotherapy + NBTXR3 in this trial showed the best control of the treated and distant untreated tumors, then any single agent or doublet combination.

NBTXR3 Potentiates Cancer-Cell Intrinsic Interferon beta Response to Radiotherapy Poster #3366 Maria Esperanza Rodriguez-Ruiz1, Karsten A Pilones1, Camille Daviaud1, Jeffrey Kraynak1, Audrey Darmon2, Sébastien Paris2 and Sandra Demaria1 1Department of Radiation Oncology, Weill Cornell Medicine, New York, USA; 2Nanobiotix, Paris, France

Data suggests that NBTXR3 enhances the effectiveness of radiation and improves tumor immunogenicity in murine breast cancer cell lines, via the induction of type-I interferon (IFN-I). In the study, NBTXR3 activated by radiotherapy amplified cancer cell intrinsic IFN-I response and showed a significant improvement in tumor control compared to radiotherapy alone with complete durable regression of tumors.-Ends

About NBTXR3

NBTXR3 is a first-in-class product candidate designed to destroy tumors and metastasis when activated by radiotherapy.

NBTXR3 has a high degree of biocompatibility and requires one single administration before the whole radiotherapy treatment. Nanobiotix believes NBTXR3 has the ability to fit into current worldwide standards of radiation care.

Nanobiotix’s broad clinical program includes seven clinical trials. In June 2018, Nanobiotix established human proof of concept for this first-in-class product candidate in its soft tissue sarcoma (STS) Phase III clinical trial. NBTXR3 is actively being studied in head and neck cancer with locally advanced squamous cell carcinoma of the oral cavity or oropharynx in elderly and frail patients who are unable to receive chemotherapy or cetuximab and have very limited therapeutic options. Promising results from these clinical studies have been observed from the ongoing Phase I/II trial regarding the local control of tumors.

Nanobiotix is also running an immuno-oncology development program. In the United States, Nanobiotix has received approval from the U.S. Food and Drug Administration to launch a clinical study of NBTXR3 activated by radiotherapy in combination with anti-PD1 antibodies in lung, and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung cancer).

The other ongoing NBTXR3 trials are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and prostate adenocarcinoma.

The first market authorization process (CE Marking) for the STS indication is ongoing in Europe

Xynomic Pharma Achieves Important Regulatory Milestones in China and EU in Potentially Pivotal Kidney Cancer and Lymphoma Trials

On April 2, 2019 Xynomic Pharma, a clinical stage US-China oncology drug development company, and Bison Capital Acquisition Corp. (Nasdaq: BCAC), reported that China, Spain and Poland authorities have approved Xynomic’s application to conduct potentially pivotal Phase 3 trial using Xynomic’s abexinostat, in combination with pazopanib, in patients with renal cell carcinoma (RCC) (Press release, Xynomic Pharmaceuticals, APR 2, 2019, View Source [SID1234534944]). Xynomic plans to initiate this trial in China, Spain, Poland and additional European countries in the first half of 2019. The same trial is currently ongoing in the United States and South Korea. According to a June 2018 research report by Grand View Research, RCC accounts for 1.8% of total adult malignancies globally and 3.4% of all new cancer cases in the United States. The global RCC pharmaceuticals market size is projected to reach US$ 4.6 billion in 2019.

In addition, the Independent Ethics Committee at the Cancer Hospital Chinese Academy of Medical Sciences in Beijing, China’s number one ranked cancer specialty hospital according to Fudan University’s Hospital Management Institute, has approved Xynomic’s application to conduct two potentially pivotal Phase 2 trials, one to test abexinostat as a third-line mono therapy against diffuse large B-cell lymphoma (DLBCL) and the other as a third-line mono therapy against follicular lymphoma (FL). According to Chinese Medical Association’s Chinese Society of Hematology, DLBCL and FL are the most prevalent and second most prevalent non-Hodgkin’s lymphoma subtype, respectively, in China.

IGEM Therapeutics announces further UK government funding to develop novel IgE antibody targeting solid tumours expressing HER2

On April 2, 2019 IGEM Therapeutics (IGEM), an immuno-oncology company developing novel immunoglobulin E (IgE) antibodies to treat cancer, reported the award of a £0.75 million grant from the UK’s innovation agency, Innovate UK (Press release, IGEM Therapeutics, APR 2, 2019, View Source [SID1234534942]). IGEM will use the Biomedical Catalyst Primer Award to develop novel IgE antibodies targeting HER2, a commercially-validated cancer antigen expressed on a variety of tumour types including breast, ovarian and gastric cancer.

Currently marketed anti-HER2 IgG antibodies are only able to treat patients with cancers expressing high levels of HER2 antigen. The majority of HER2 positive patients have cancers expressing intermediate or low levels of HER2 and cannot be treated with anti-HER2 IgG antibodies. To address this substantial unmet medical need, IGEM is developing novel, human IgE antibodies that bind to HER2.

The epsilon constant region of IgE has evolved to fight complex, multicellular parasitic organisms resident in tissue by recruiting powerful immune effector cells such as macrophages, basophils and monocytes. IGEM believes that potent immune responses arising from IgE are suited to the destruction of solid tumours which also reside in tissue. Pre-clinical studies in the laboratory of IGEM Founder Dr Sophia Karagiannis at King’s College London have demonstrated superior efficacy with a number of IgE antibodies when compared to their IgG equivalents. IGEM is also developing anti-cancer IgE antibodies targeting folate receptor alpha and CSPG-4.

Dr Tim Wilson, Chief Executive Officer of IGEM, commented: "IGEM is a pioneer in the use of IgE antibodies to treat cancer. We are very pleased to have been awarded our second grant from Innovate UK. Our goal is to harness the potency of the IgE-mediated immune response and thereby provide patients with new safe and effective treatment options for these serious diseases".

Geron to Present at Needham Healthcare Conference

On April 2, 2019 Geron Corporation (Nasdaq: GERN) reported that John A. Scarlett, M.D., Chairman and Chief Executive Officer, is scheduled to present a company overview at the 18th Annual Needham Healthcare Conference in New York at 3:30 p.m. ET on Tuesday, April 9, 2019 (Press release, Geron, APR 2, 2019, View Source [SID1234534940]).

A live audio webcast of the presentation will be available on Geron’s website, www.geron.com/investors/events. If you are unable to listen to the live presentation, an archived webcast will be available on the Company’s website for 30 days.