On June 3, 2019 Incyte (Nasdaq:INCY) reported primary efficacy results from the Novartis-sponsored GEOMETRY mono-1 Phase 2 clinical trial of capmatinib, an investigational, selective MET inhibitor (Press release, Incyte, JUN 3, 2019, View Source [SID1234536781]). The results demonstrate that capmatinib shows promise as a potential treatment option for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbor a MET exon-14 skipping mutation. There are currently no approved targeted therapies to treat this particularly aggressive form of NSCLC.

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Results of the Phase 2 study will be presented at an oral session today, June 3, 2019, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2019 Annual Meeting at 8:00 a.m. CDT (Abstract #9004)1.

GEOMETRY mono-1 is an international, prospective, multi-cohort, non-randomized, open-label study evaluating 97 adult patients with locally advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation who received capmatinib tablets 400 mg orally twice daily. Primary efficacy results among treatment-naïve patients (Cohort 5b: 28 patients) included a 68 percent overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1 (95% [CI: [47.6-84.1]) and 41 percent of previously-treated NSCLC patients (Cohort 4: 69 patients) also responded (95% CI: [28.9 – 53.1]). Data on median duration of response (DOR), a key secondary endpoint, was 11.14 months (95% CI: [5.55-NE]) and 9.72 months (95% CI: [5.55-12.98]), in the treatment-naïve and previously-treated groups, respectively. Intracranial activity in 54 percent (n=7/13) of patients, including some cases of complete resolution of brain lesions, was also observed by ad hoc neuro-radiologist review in patients with brain lesions. All results were based on independent assessment by the BIRC, and all tumor CT scans were evaluated in parallel by two radiologists to confirm the response.

The most common treatment-related adverse events (AE) (≥10% all grades) across all cohorts (n=334), were peripheral edema (42%), nausea (33%), creatinine increase (20%), vomiting (19%), fatigue (14%), decreased appetite (13%) and diarrhea (11%); the majority of the AEs were grades 1/2.

"In the absence of approved targeted therapies, patients with advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation must rely on existing treatment approaches and, as a result, face a particularly poor prognosis," said Steven Stein, M.D., Chief Medical Officer, Incyte. "The results of the GEOMETRY mono-1 study to be presented at ASCO (Free ASCO Whitepaper) underscore the potential of capmatinib to meaningfully improve outcomes for this underserved subset of NSCLC patients."

The U.S. Food and Drug Administration (FDA) recently granted capmatinib Breakthrough Therapy designation for patients with metastatic NSCLC harboring a MET exon-14 skipping mutation with disease progression on or after platinum-based chemotherapy. Previously, both the U.S. FDA and Japan’s Pharmaceuticals and Medical Devices Agency recognized capmatinib with Orphan Drug status. It is estimated that 3 to 4 percent of all patients with NSCLC have an identified MET mutation2.

Novartis expects to submit a new drug application to the FDA for capmatinib as a treatment for patients with advanced NSCLC harboring a MET mutation in 2019.

About GEOMETRY mono-1

The Novartis-sponsored GEOMETRY mono-1 trial is an international, prospective, multi-cohort, non-randomized, open-label Phase 2 study to evaluate the efficacy and safety of single-agent capmatinib in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring a MET amplification and/or mutation. Patients with locally advanced or metastatic NSCLC harboring a MET exon-14 skipping mutation (centrally confirmed) were assigned to Cohorts 4 (previously treated patients) or 5B (treatment-naïve), regardless of MET amplification/gene copy number and received 400 mg capmatinib tablets orally twice daily.

The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was DOR by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naïve patients (n=28) of 67.9 percent (95% CI: [47.6 – 84.1]) and an ORR of 40.6 % (95% CI: [28.9 – 53.1]) in the previously treated patients (n=69). Median DOR was 11.14 months (95% CI: [5.55-NE]) in treatment-naïve patients and 9.72 months (95% CI: [5.55-12.98]) in previously treated patients1.

The most common treatment-related AEs included peripheral edema, nausea, creatinine increase and vomiting. Of patients treated with capmatinib, 84 percent experienced an AE, with 36 percent having grade 3/4 AEs (only 4.5% were Grade 4)1.

About Capmatinib

Capmatinib is an investigational, oral and selective MET inhibitor discovered by Incyte that was licensed to Novartis in 2009. Under the terms of the Agreement, Incyte granted Novartis exclusive worldwide development and commercialization rights to capmatinib and certain back-up compounds in all indications. If capmatinib is successfully developed by Novartis, Incyte may become eligible for over $500 million in future milestones as well as royalties of between 12 and 14 percent on global sales by Novartis.

On June 2, 2019, Corvus Pharmaceuticals presented the corporate presentation (Presentation, Corvus Pharmaceuticals, JUN 2, 2019, View Source [SID1234536804]).

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On June 2, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that preliminary results from the dose escalation part of a phase 1 study with DS-1062, an investigational TROP2 targeting antibody drug conjugate (ADC), in 39 patients with advanced non-small cell lung cancer (NSCLC) were presented today during a Poster Session at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Abstract #9051) (Press release, Daiichi Sankyo (Brazil), JUN 2, 2019, https://www.prnewswire.com/news-releases/daiichi-sankyo-presents-preliminary-phase-1-data-for-trop2-targeting-adc-ds-1062-in-patients-with-non-small-cell-lung-cancer-at-2019-asco-annual-meeting-300860250.html [SID1234536785]).

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Preliminary efficacy data for 35 evaluable patients who received DS-1062 at the dose levels between 0.27 mg/kg and 8.0 mg/kg every 21 days showed three confirmed and four not yet confirmed partial responses at the time of data cut-off on April 12, 2019.

An additional three partial responses have been reported with the 8.0 mg/kg dose of DS-1062 since data cut-off, bringing the total partial responses to 10. The median number of prior therapies for the partial responders is 3.5 and includes patients with prior EGFR or ALK inhibitors and checkpoint inhibitors. A maximum tolerated dose of DS-1062 has not yet been reached and the dose escalation portion of the study is ongoing. Sixteen patients remain on-treatment at the time of data cut-off.

"Despite recent advances in the treatment of NSCLC, we need new precision treatment options for patients with advanced disease who currently have no available standard treatment options," said Jacob Sands, MD, Physician, Dana-Farber Cancer Institute, Instructor, Harvard Medical School, and lead investigator for the study. "These early results are encouraging as we have seen increased activity with higher doses of DS-1062 including several partial responses. Additional study is warranted to further determine the potential for targeting TROP2 with DS-1062 in these patients with advanced NSCLC."

Preliminary data for 39 patients evaluable for safety as of April 12, 2019 showed that DS-1062 was well-tolerated at a median treatment exposure time of 8.86 weeks (range 3.0-31.1). Common treatment emergent adverse events (occurring in ≥ 30 percent of patients) included fatigue (33.3 percent) and nausea (30.8 percent). Sixteen patients (41.0 percent) experienced at least one treatment emergent adverse event ≥ grade 3. One dose-limiting toxicity of maculopapular rash, grade 3 was observed in a patient in the 6.0 mg/kg cohort. Ten patients (25.6 percent) experienced serious adverse events not related to study drug, and one patient (2.5 percent) in the 4.0 mg/kg cohort experienced a treatment-related serious adverse event of pyrexia.

"We are encouraged by these preliminary results with DS-1062, which was designed using our proprietary DXd ADC technology to target and deliver treatment directly to tumors that express TROP2, a promising therapeutic target for many types of cancer, including NSCLC," said Eric Slosberg, PhD, Head, Global Translational Development, Oncology Research and Development, Daiichi Sankyo. "Currently, there are no TROP2 targeting therapies approved for any cancer, and we will continue to study DS-1062 as part of our commitment to developing new targeted therapy options for patients with non-small cell lung and other cancers."

DS-1062 is designed using Daiichi Sankyo’s proprietary DXd ADC technology, which consists of a humanized monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. DS-1062 was designed to target and deliver chemotherapy inside cancer cells that express TROP2 as a cell surface antigen. The DXd ADC technology provides flexibility to adapt the drug-to-antibody ratio (DAR) or the number of DXd molecules conjugated per antibody. DS-1062 has a DAR of four, which is based on initial research into the construct necessary for intended efficacy and safety in TROP2 expressing tumors.

About the Phase 1 Study
The phase 1, first-in-human open-label study is investigating the safety and tolerability of DS-1062 in patients with unresectable advanced NSCLC who are refractory to or have relapsed following standard treatment or for whom no standard treatment is available. The first part of the study (dose escalation) is assessing the safety and tolerability of increasing doses of DS-1062 to determine the maximum tolerated dose and recommended dose for expansion. The second part of the study (dose expansion) will evaluate the safety and tolerability of DS-1062 at the recommended dose for expansion. Study endpoints include safety, pharmacokinetics, objective response rate, duration of response, disease control rate, time to response, progression-free survival, overall survival, biomarker analysis and immunogenicity. The study is currently enrolling patients with unresectable advanced NSCLC in the United States and Japan.

Based on the results of the study, additional cohorts may be initiated for other solid tumors where high expression of TROP2 is frequently observed. For more information about the study, visit ClinicalTrials.gov.

Unmet Need in Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide; there were an estimated 2.1 million new cases of lung cancer in 2018 and 1.8 million deaths.1 Most lung cancers are diagnosed at an advanced or metastatic stage.2 Non-small cell lung cancer (NSCLC) accounts for 80 to 85 percent of all lung cancers.3 The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic NSCLC; however, for those who are not eligible for current treatments, or whose cancer continues to progress, new therapeutic approaches are needed.4

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is highly expressed on several types of solid tumors, including NSCLC.5,6 Researchers have recognized TROP2 as a promising molecular target for therapeutic development in various types of malignancies, including NSCLC.6,7 Overexpression of TROP2 has been associated with increased tumor aggressiveness and decreased survival in several cancers.8 High TROP2 expression was identified in 64 percent of non-small cell adenocarcinomas and 75 percent of non-small cell squamous cell carcinomas in one study.5 Currently, no TROP2 targeting therapy is approved for NSCLC or any cancer.

About DS-1062
Part of the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise, DS-1062 is an investigational TROP2 targeting ADC. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, DS-1062 is comprised of a humanized anti-TROP2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-1062 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: [fam-] trastuzumab deruxtecan, an antibody drug conjugate (ADC) for HER2 expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory FLT3-ITD acute myeloid leukemia (AML); and pexidartinib, an oral CSF1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com.

On June 2, 2019 BerGenBio ASA (OSE: BGBIO) a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported data from its Phase II clinical trial (BGBC008, NCT03184571) with bemcentinib and Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced non-small cell lung cancer (NSCLC) at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Illinois (31 May – 4 June 2019) (Press release, BerGenBio, JUN 2, 2019, View Source;median-survival-rates-in-phase-ii-trial-with-bemcentinib-and-keytruda-in-pts-with-advanced-nsclc-at-asco-2019-300860276.html [SID1234536784]).

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At data cut off, 35 out of 46 enrolled patients were evaluable; 58% were AXL +ve, and 53% were PD-L1 negative (<1%TPS), and a further 39% were PD-L1 (1-49% TPS). An objective response rate of 40% was achieved in AXL +ve patients, irrespective of the patients PD-L1 score; and an overall response rate of 29% was achieved. The median survival rate of 12.2 months was observed at the time of data cut-off, significantly surpassing what has been shown historically in second line treatment with PD-1 inhibitor monotherapy.

The combination treatment of bemcentinib and pembrolizumab was overall well-tolerated; the most common adverse events included transaminase increase (35%), fatigue (30%), and diarrhoea (26%). No grade 5 treatment related adverse events were reported and all events were reversible.

Principal investigator Enriqueta Filip, Vall d’Hebron University Hospital, Barcelona: "Following the rapid uptake of checkpoint inhibitors in first-line lung cancer therapy, treatment options for NSCLC cancer patients that have not responded to anti-PD-1 therapies such as KEYTRUDA represent a significant unmet medical need. These data, which suggest that combination therapy with bemcentinib has the potential to enhance patient responses to these novel agents, particularly in patients with no or limited expression of PD-L1, is a very significant and encouraging development."

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "The clinical activity we are presenting here today surpasses what has been shown historically in previously-treated, PD-L1 low patients on PD-1 inhibitor monotherapy, and supports the hypothesis that AXL is implicated in the failure of anti-PD-L1 therapies. Further investigation is warranted and having recently extended the trial to include patients showing disease progression on checkpoint inhibitors, we will continue to test this hypothesis and look forward to providing further updates during 2019."

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 non-small cell lung cancers (NSCLC) 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.

On June 2, 2019 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines, reported that the study results for efficacy and safety of IBI305 (biosimilar of bevacizumab) compared with bevacizumab in advanced, first-line, non-squamous NSCLC patients (NCT02954172) were presented by poster at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) [Abstract #9095; Sunday, June 2, 8:00 AM – 11:00 AM CDT] (Press release, Innovent Biologics, JUN 2, 2019, View Source [SID1234536783]).

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As the top and most influential international oncology conference, ASCO (Free ASCO Whitepaper) Annual Meeting provides the most important platform for publishing and discussing cutting edge clinical studies. Under the theme "Caring for Every Patient, Learning from Every Patient", 2019 ASCO (Free ASCO Whitepaper) Annual Meeting has attracted numerous top oncologists, scholars, staff from regulatory and patient organizations to share the latest updates and achievements in clinical oncology, with the ultimate goal to help deliver more promising medicines and treatment options to cancer patients.

It is worth noting that more and more Chinese companies choose to participate and disclose their programs in ASCO (Free ASCO Whitepaper), showcasing the importance of emerging Chinese biotech industry. As a leading Chinese biotech company, Innovent will provide key result update of several clinical studies at the ASCO (Free ASCO Whitepaper) 2019 Annual Meeting. The results on the treatment of relapsed or refractory extranodal NK/T cell lymphoma (ORIENT-4) with sintilimab will be presented in an oral session, and key data from several other clinical studies will be presented by posters and other sessions.

IBI305 is a recombinant humanized anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody developed by Innovent for the treatment of non-small cell lung cancer (NSCLC), colorectal cancer and other malignant tumors. Bevacizumab (marketed under the trade name Avastin in China) has been approved globally for the treatment of multiple types of malignant tumors including NSCLC and has a favorable safety and efficacy profile. In 2012, bevacizumab was approved in China. Despite the huge demand for effective cancer therapies, the adoption rate of bevacizumab is relatively low due to low affordability.

NCT02954172 study, led by Professor Li Zhang from Sun Yat-sen University Affiliated Cancer Hospital, is a multicenter, randomized, double-blind, parallel, active-controlled, Phase III study in China, evaluating the efficacy and safety of IBI305 (biosimilar product candidate of bevacizumab) compared with bevacizumab in advanced non-squamous NSCLC patients as first-line treatment with ORR as the primary endpoint.

Among 450 recruited patients in the NCT02954172 study, there are 224 patients in IBI305 cohort and 226 patients in bevacizumab cohort.

The ORRs, evaluated by the Independent Radiological Review Committee (IRRC) in the full analysis set (FAS), were 44.3% (98/221) for IBI305 and 46.4% (102/220) for bevacizumab; the relative risk (RR) for ORR was 0.95 (90% CI: 0.803, 1.135).
The median progression free survival (PFS) was 7.9 months for IBI305 and 7.8 months for bevacizumab and duration of response (DoR) was also similar in both arms.
Treatment-emergent adverse events (TEAEs) were well balanced between treatment arms and consistent with the known adverse event profile of reference bevacizumab.
Based the outcome of the study, the new drug application (NDA) of IBI305 was accepted by the NMPA in January 2019 and has been granted priority review status.

Innovent intends to introduce a more affordable, high-quality biosimilar of bevacizumab to reach more patients in China and to further relieve their disease burden, benefiting more patients and their families.

About IBI305 (bevacizumab biosimilar)

IBI305 is a biosimilar product candidate of bevacizumab and a recombinant humanized anti-VEGF monoclonal antibody for injection. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF selectively with high affinity and blocks its binding to VEGF receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. Bevacizumab produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. The new drug application (NDA) of IBI305 was accepted by the NMPA on January 29, 2019 and has been granted with priority review status.