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 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 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive additional results of a prespecified exploratory analysis from the Phase III IMpower150 study, which demonstrated that the combination of Tecentriq (atezolizumab), Avastin (bevacizumab), carboplatin and paclitaxel (chemotherapy) gave patients with chemotherapy-naïve, metastatic non-squamous non-small cell lung cancer (NSCLC), with baseline liver metastases an overall survival (OS) advantage compared with the combination of Avastin and chemotherapy (median OS=13.3 vs 9.4 months; hazard ratio [HR]=0.52; 95% CI: 0.33–0.82) in the intention-to-treat (ITT) population.1 Safety for the Tecentriq, Avastin, and chemotherapy combination appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination (Press release, Hoffmann-La Roche, JUN 2, 2019, View Source [SID1234536754]).

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"We are pleased to present further positive results from the Phase III IMpower150 study that show benefit in people with baseline liver metastases, a population with a worse prognosis for survival", said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Initial treatment with Tecentriq, Avastin and chemotherapy may represent an important new option for people with baseline liver metastases, as their risk of disease worsening or death was reduced by more than half and 60% responded to the combination treatment".

These data will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting on Sunday, 2 June 2019 at 16:30–18:00 CDT (Abstract #9012).

In December 2018, the US Food and Drug Administration approved Tecentriq in combination with Avastin, carboplatin and paclitaxel for the first-line treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations. This approval was based on positive data from Arm B of the Phase III IMpower150 study, which showed that Tecentriq and Avastin plus carboplatin and paclitaxel helped people live significantly longer compared with Avastin plus carboplatin and paclitaxel (median OS=19.2 vs 14.7 months; HR=0.78; p=0.016) in the intention-to-treat wild-type (ITT-WT) population.2

In March 2019, the European Commission also approved and granted marketing authorisation for Tecentriq in combination with Avastin, paclitaxel and carboplatin for the first-line treatment of adults with metastatic non-squamous NSCLC. In people with EGFR-mutant or ALK-positive NSCLC, Tecentriq, in combination with Avastin, paclitaxel and carboplatin, is indicated only after failure of appropriate targeted therapies. This approval was based on positive data from Arm B of the Phase III IMpower150 study, which showed that Tecentriq and Avastin plus carboplatin and paclitaxel helped people live significantly longer compared with Avastin plus carboplatin and paclitaxel (median OS=19.8 vs 14.9 months; HR=0.76; 95% CI: 0.63–0.96; p=0.006) in the ITT population.3

About the IMpower150 study
IMpower150 is a multicentre, open-label, randomised, controlled Phase III study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV or recurrent metastatic non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease. A total of 1,202 people were enrolled, of whom 1,045 were in the ITT-WT subpopulation, which excluded those people with EGFR and ALK mutations. People were randomised (1:1:1) to receive:

Tecentriq plus carboplatin and paclitaxel (Arm A), or
Tecentriq and Avastin plus carboplatin and paclitaxel (Arm B), or
Avastin plus carboplatin and paclitaxel (Arm C, control arm).
The co-primary endpoints comparing Arms B and C were OS and progression-free survival (PFS), as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) and assessed in the ITT-WT subpopulation. Key secondary endpoints included investigator-assessed PFS, OS and safety in the ITT population. Exploratory analyses included efficacy and safety in people with baseline liver metastases.

A summary of the ITT data for the liver metastases population (a prespecified exploratory subgroup) from the IMpower150 study is included below:1

A survival advantage was observed in people who received Tecentriq in combination with Avastin and chemotherapy, compared with Avastin and chemotherapy alone (median OS=13.3 vs 9.4 months; HR=0.52; 95% CI: 0.33–0.82).
In addition, Tecentriq, Avastin and chemotherapy reduced the risk of disease worsening or death (PFS) by 59%, compared with Avastin and chemotherapy (HR=0.41; 95% CI: 0.26–0.62).
Tecentriq, Avastin and chemotherapy shrank tumours (overall response rate) in 60.8% of people (95% CI: -0.75–40.18) compared with 41.1% of people receiving Avastin and chemotherapy.
The median duration of response for people receiving Tecentriq, Avastin and chemotherapy was 10.7 months (95% CI: 0.21–0.73) compared with 4.6 months for people on Avastin and chemotherapy.
Grade 3–4 treatment-related adverse events occurred in 52.1% and 54.5% of patients with liver metastases in Arm B and Arm C, respectively.
About NSCLC
Lung cancer is the leading cause of cancer death globally.4 Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.4 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.5 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.5 Typically, 15–20% of NSCLC cases will also present with liver metastasis, which are difficult-to-treat; these patients have a poorer prognosis, with an approximately 50% increased risk of death.6 In addition, patients with liver metastases are more likely to have other metastases in the body.7

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

In the United States, Tecentriq in combination with nab-paclitaxel is approved for treatment of PD-L1-positive metastatic triple-negative breast cancer; and in combination with Avastin and chemotherapy for the initial treatment of people with metastatic non-squamous NSCLC. Tecentriq is also approved in the United States as an initial treatment for extensive-stage small cell lung cancer (ES-SCLC). In the Europe Union, the non-squamous NSCLC indication includes people with EGFR mutant or ALK genomic tumour aberrations after failure of appropriate targeted therapies. Tecentriq is also approved in the European Union, United States and more than 90 countries for people with previously treated metastatic non-small cell lung cancer (NSCLC) and for certain types of untreated or previously treated metastatic urothelial carcinoma.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

About the Tecentriq (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat first-line advanced NSCLC. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

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 Amgen (NASDAQ: AMGN) reported new data from Phase 1 studies evaluating investigational bispecific T cell engager (BiTE) molecules were presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (Press release, Amgen, JUN 2, 2019, View Source;p=RssLanding&cat=news&id=2400287 [SID1234536742]). Data presented included updated investigational AMG 420 safety and efficacy results in patients with relapsed and/or refractory multiple myeloma (R/R MM), as well as initial results from the investigational AMG 212 (pasotuxizumab) first-in-human trial in patients with metastatic castration-resistant prostate cancer (mCRPC). BiTE technology is a targeted immuno-oncology platform that is designed to engage patients’ own T cells to a tumor-specific antigen, activating the cytotoxic potential of T cells.

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"Our BiTE immuno-oncology platform offers unique versatility, with the potential to treat various tumors through targeting tumor-associated antigens," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "As a leader in the development of targeted immuno-oncology therapies, we continue to investigate and advance more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors. These data at the ASCO (Free ASCO Whitepaper) Annual Meeting reinforce the potential of BiTE technology for patients with difficult-to-treat cancers like multiple myeloma and prostate cancer."

ASCO Annual Meeting Abstract #8007: Evaluation of AMG 420, An Anti-BCMA Bispecific T Cell Engager (BiTE) Immunotherapy, In R/R Multiple Myeloma (MM) Patients: Updated Results of a First-in-Human (FIH) Phase 1 Dose-Escalation Study

Updated results from a Phase 1, first-in-human dose-escalation trial of investigational AMG 420, a B-cell maturation antigen (BCMA)-targeting BiTE molecule, in patients with R/R MM were shared during an oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting. This abstract was also selected for inclusion in the Best of ASCO (Free ASCO Whitepaper) educational program. The objectives of the study included assessment of the safety, tolerability and anti-tumor activity of AMG 420 per International Myeloma Working Group 2006 Uniform Response Criteria for Multiple Myeloma. In the study, 42 patients with R/R MM who had progression after at least two prior lines of treatment (including a proteasome inhibitor and an immunomodulatory imide drug) received AMG 420 at varying doses [0.2 to 800 µg/day (d)]. Of the doses tested in this study, 400 µg/d was the maximum tolerated dose (MTD).

As of the latest readout, AMG 420 induced clinical responses in 13 of 42 patients across the dosing cohorts. Of the six patients that achieved a minimal residual disease (MRD)-negative complete response (CR), five were treated at the 400 µg/d dose. In addition, at the 400 µg/d dose, one patient achieved a very good partial response, and one achieved a partial response. The overall response rate at 400 µg/d was 70 percent (7/10). The median duration of response was nine months (range 5.8-13.6 months). Median time to response was one month, with 11 of 13 patients responding in the first cycle.

Serious adverse events (AEs) were reported in 19 patients (45 percent). Sixteen required hospitalization and four had prolonged hospitalization. No grade 3 or 4 central nervous system toxicities were observed. Serious AEs occurring in more than one patient included infections (n=13) and peripheral polyneuropathy (n=2). Treatment-related serious AEs included polyneuropathy (n=2, both grade 3) and edema (n=1, grade 3). Grade 3 cytokine release syndrome (CRS) was seen in one patient. Two patients died during the study from AEs not considered treatment-related: one patient died from acute respiratory distress due to concurrent flu and aspergillosis, and the second patient died from liver failure secondary to a viral infection during the course of treatment.

"These updated results presented at the ASCO (Free ASCO Whitepaper) Annual Meeting showed that AMG 420 at the 400 µg/d dose was efficacious with no new safety concerns in heavily pre-treated patients with relapsed and/or refractory multiple myeloma," said Max S. Topp, M.D., professor, University Hospital of Wuerzburg, Germany, and AMG 420 clinical study investigator. "Based on these results, we recommend AMG 420 at the 400 µg/d dose for further investigation."

ASCO 2019 Abstract #5034: Phase 1 Study of Pasotuxizumab (BAY 2010112), a PSMA-targeting BiTE (Bispecific T Cell Engager) Immunotherapy for Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Initial results from a Phase 1 dose-escalation study of investigational AMG 212 (pasotuxizumab, formerly known as BAY 2010112), in patients with mCRPC who are refractory to standard therapy were presented in a poster at the ASCO (Free ASCO Whitepaper) Annual Meeting. AMG 212 is an investigational BiTE molecule which is designed to target prostate-specific membrane antigen (PSMA), a promising target in mCRPC. In the trial, 16 patients with mCRPC were enrolled into five dosing cohorts, with a target dose range of 5 to 80 µg/d delivered by continuous intravenous infusion. The primary objective was to determine safety and MTD and secondary objectives included pharmacokinetics (PK), biomarkers and tumor response. Antitumor activity as indicated by decline in serum level of prostate-specific antigen (PSA) was dose dependent. PSA decreases of ≥ 50 percent occurred in three patients (n=1 each in 20 µg/d, 40 µg/d and 80 µg/d cohorts). One long-term responder was treated for 14 months (40 µg/d) and one for 19.4 months (80 µg/d). The latter patient showed a complete regression of soft-tissue metastases and marked regression of bone metastases, as well as a significant and durable improvement in disease-related symptoms. Recruitment in the trial was stopped before MTD was reached to facilitate initiation of a new study sponsored by Amgen.

"Metastatic castrate-resistant prostate cancer is considered a heterogenous disease and despite advances made over the last few years, the majority of patients face a poor outlook1," said Horst-Dieter Hummel, M.D., University Hospital of Wuerzburg, Germany, and AMG 212 clinical study investigator. "In the first clinical study investigating the potential of a BiTE molecule in solid tumors, AMG 212 showed clinical activity, including two long-term responders. We look forward to studying AMG 212 further in this patient population."

The most common drug-related AEs were fever (94 percent, n=15) and chills (69 percent, n=11). A drug-related serious AE (fatigue) was reported in one patient. CRS was reported for three patients (19 percent); two were grade 2 and one was grade 3. No grade 5 AEs occurred.

Additional Updates on Amgen’s BiTE Immuno-Oncology Platform at ASCO (Free ASCO Whitepaper) 2019
Amgen continues to investigate the BiTE immuno-oncology platform across a broad range of solid and hematologic malignancies with the goal of enhancing patient experience and therapeutic potential. Amgen is investigating more than a dozen BiTE molecules across a range of solid and hematologic malignancies, with an additional two trials-in-progress being presented at the ASCO (Free ASCO Whitepaper) Annual Meeting.

During poster sessions, researchers shared information on the studies of AMG 596, an investigational BiTE molecule targeting epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (GBM), and AMG 757, an investigational BiTE molecule targeting delta-like ligand 3 (DLL3) in small-cell lung cancer (SCLC). GBM and SCLC are both aggressive and difficult-to-treat forms of cancer where there is a significant unmet medical need for patients.

Forty-three percent of GBM tumors test positive for amplification or mutation of the EGFR, the most common of which is the EGFRvIII gain-of-function mutation.2 A Phase 1, first-in-human, open-label, sequential dose-escalation and dose-expansion study is ongoing for investigational AMG 596, evaluating its safety, tolerability, and PK and pharmacodynamics in patients with EGFRvIII-postive glioblastoma. The study is expected to enroll 82 patients in two groups: one with recurrent GBM and a second in newly diagnosed patients in the maintenance treatment phase following standard of care treatment.

DLL3 is an inhibitory ligand of notch receptors that is expressed in most SCLC tumors but minimally expressed in normal tissues.3 An ongoing open-label, ascending, multiple-dose, Phase 1 study is evaluating investigational AMG 757 in adult patients with SCLC which has progressed or recurred after at least one platinum-based chemotherapy regimen. Primary objectives are to evaluate safety and tolerability and to determine the MTD or recommended Phase 2 dose. Secondary objectives are to characterize PK and evaluate preliminary anti-tumor activity.

For more information on these and other ongoing clinical trials, visit www.AmgenTrials.com.

Amgen Webcast Investor Meeting
Amgen will host a webcast investor meeting at ASCO (Free ASCO Whitepaper) 2019 on Monday, June 3 at 6:30 p.m. CT. David M. Reese, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team and clinical investigators, will participate at the investor meeting to discuss Amgen’s oncology program and data presented at ASCO (Free ASCO Whitepaper) 2019.

Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given at certain investor and medical conferences, can be accessed on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About BiTE Technology
BiTE (Bispecific T cell engager) technology is a targeted immuno-oncology platform that is designed to engage patients’ own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells with the goal of eliminating detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has the goal of off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of solid and hematologic malignancies, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential.