On September 21, 2020 DCprime, the front-runner in the field of relapse vaccines, and Glycotope GmbH, a clinical-stage oncology/immuno-oncology company built on world-leading glycobiology expertise, reported an expansion of their existing partnership through a new research collaboration and licensing agreement (Press release, DCPrime, SEP 21, 2020, View Source [SID1234565389]).

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Originally initiated in July 2018, the partnership combines DCprime’s proprietary DCOne relapse vaccine platform and Glycotope’s highly specific anti-tumor antibody platform with the aim of developing novel immunotherapeutic approaches in oncology. Under the expanded agreement a therapeutic antibody program has been selected from Glycotope’s portfolio which will be further evaluated in preclinical studies to potentially treat a broad range of solid tumors.

"Today’s agreement further exemplifies our commitment to develop novel cancer immunotherapies based on partnerships, in addition to pioneering the relapse vaccine paradigm. Our relationship with Glycotope has matured and brought forward a very promising program, potentially leading to a highly differentiated novel combination therapy towards solid tumors," commented Erik Manting, CEO of DCprime.

"We are delighted to expand our collaboration with DCprime and to see one of our antibody programs move forward in a novel combination therapy approach with a cancer vaccine based on the DCOne platform," said Henner Kollenberg, Managing Director of Glycotope GmbH. "Glycotope has developed a growing pipeline of high-value cancer therapies and today’s announcement further highlights the promising product opportunities for monotherapeutic or combinational approaches offered by our portfolio."

On September 20, 2020 Amgen (NASDAQ: AMGN) reported that updated data from the full Phase 1 cohort of the CodeBreaK 100 clinical study, evaluating sotorasib (proposed INN for AMG 510) in 129 patients across multiple advanced solid tumors, were published in the New England Journal of Medicine (NEJM) (Press release, Amgen, SEP 20, 2020, View Source [SID1234565397]). Data from 59 patients with advanced non-small cell lung cancer reported in the NEJM manuscript were also featured today during an oral presentation at ESMO (Free ESMO Whitepaper) 2020.

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"CodeBreaK 100 is the largest Phase 1/2, and first-in-human, clinical study for a KRASG12C inhibitor," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Earlier this year at ASCO (Free ASCO Whitepaper), we reported encouraging early data in patients with advanced colorectal cancer and a number of other solid tumors. We’re pleased to share these updated Phase 1 results, particularly in patients with advanced non-small cell lung cancer, and look forward to the Phase 2 readout in this heavily pretreated population later this year."

Sotorasib demonstrated confirmed objective response rate (ORR) and disease control rates (DCR) of 35.3% and 91.2%, respectively, in 34 heavily pretreated patients (median of two prior lines of therapy) with NSCLC, who were treated with the 960 mg daily dose (data cutoff of June 1, 2020).

Anticancer activity was seen across all dose levels in patients with NSCLC, with a confirmed ORR of 32.2% and DCR of 88.1%, and median duration of response of 10.9 months, with 10 of 19 responders still in response as of the data cutoff. Tumor shrinkage was observed in 71.2% of patients at the first week-6 assessment. Median progression-free survival (mPFS) in patients treated with sotorasib was 6.3 months.

Safety and tolerability in patients with NSCLC were consistent with previously seen CodeBreaK 100 results. No dose-limiting toxicities were observed and there were no fatal treatment-related adverse events (TRAEs). The most common TRAEs were diarrhea (25.4%), alanine aminotransferase (ALT) increase (20.3%), aspartate aminotransferase (AST) increase (20.3%), fatigue (10.2%) and nausea (10.2%). Eleven (18.6%) patients had grade 3 or higher TRAEs, one of whom had grade 3 TRAEs of ALT and AST increases that led to discontinuation of treatment.

"These latest results show that sotorasib continues to demonstrate encouraging clinical benefit in heavily pretreated patients with KRAS G12C-mutant tumors," said lead author David S. Hong, M.D., Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, TX. "The results also establish a compelling trend in tumor shrinkage and median progression-free survival with a positive benefit-risk profile."

The ESMO (Free ESMO Whitepaper) oral presentation included Phase 1 NSCLC results published in NEJM, as well as data on potential biomarkers of response to sotorasib that demonstrated clinical activity across a range of KRAS G12C mutant allele frequencies (MAFs), PD-L1 tissues expression levels, tumor mutational burden (TMB) plasma levels and tissue co-mutational profiles.

"KRAS G12C is a driver of multiple solid tumor types and is particularly prevalent in non-small cell lung cancer," said Fabrice Barlesi, M.D., Ph.D., Professor of Medicine at Aix-Marseille University, Medical Director of Gustave Roussy Institute, Paris, France. "Despite this, there are currently no approved targeted therapy options for KRAS G12C and patients remain in need of additional treatment options, which makes these new findings particularly important."

Amgen Webcast Investor Call
Amgen will host two webcast calls for the investment community in conjunction with the ESMO (Free ESMO Whitepaper) Virtual Congress 2020. On Sunday, Sept. 20, 2020, at 11:00 a.m. PDT, 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 discuss Phase 1 data being presented on the Company’s investigational KRASG12C inhibitor sotorasib (AMG 510). On Monday, Sept. 21, at 1:00 p.m. PDT, David M. Reese, M.D., along with members of Amgen’s clinical development team, will discuss the Phase 1 data being presented on the Company’s investigational half-life extended bispecific T-cell engager (BiTE) immuno-oncology therapy targeting prostate-specific membrane antigen (PSMA). 

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 KRAS
The RAS gene family, which has been the subject of almost four decades of research, contains some of the most frequently mutated oncogenes in human cancers.1,2 Targeting the KRAS protein, the most commonly altered family member in solid tumors, has been one of the toughest challenges in cancer research.1 A specific mutation known as KRAS G12C, is a major driver of tumor growth, occurring broadly across solid tumor indications. In the U.S., about 13% of patients with non-small cell lung cancer harbor the KRAS G12C mutation.3,4 It is also found in approximately 3-5% of colorectal cancers and 1-2% of numerous other solid tumors, making this among the most broadly represented mutations across cancer patient subgroups.5,6,7,8,9. With the discovery of a unique surface groove in the KRASG12C protein, Amgen developed and advanced the first investigational KRASG12C inhibitor into the clinic and is exploring the potential of KRASG12C inhibition across multiple tumor types for patients who remain in dire need of treatment options.1,10

About CodeBreaK
The CodeBreaK clinical trial program for Amgen’s investigational drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 1 study is safety, and key secondary endpoints include objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts: 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.

Amgen’s single-arm Phase 2 trials in both non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) (also part of CodeBreaK 100) are now fully enrolled. The potentially registrational Phase 2 trial in NSCLC is on track for data readout later in 2020 and a global Phase 3 randomized active-controlled confirmatory study comparing sotorasib to docetaxel in NSCLC (CodeBreaK 200) has begun recruiting. The Phase 2 CRC trial is expected to have a data readout in 2021. Amgen is also currently enrolling six Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101).

Additional information about CodeBreaK clinical trials can be found at View Source

About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

To learn more about Amgen’s innovative pipeline with diverse modalities and genetically validated targets, please visit AmgenOncology.com. For more information, follow us on www.twitter.com/amgenoncology.

On September 20, 2020 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported with Eli Lilly and Company ("Lilly",NYSE: LLY) that biomarker results from the ORIENT-11 study were released in a mini oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 (Press release, Innovent Biologics, SEP 20, 2020, View Source [SID1234565396]). The ORIENT-11 primary clinical results were released during the IASLC World Conference on Lung Cancer (WCLC) 2020 Virtual Presidential Symposium as an oral presentation and simultaneously published by the Journal of Thoracic Oncology.

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ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating TYVYT (sintilimab injection) or placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy as a first-line treatment for advanced or recurrent nonsquamous non-small cell lung cancer (nsqNSCLC) without sensitizing EGFR mutations or ALK rearrangements. The National Medical Products Administration (NMPA) of China has accepted the supplemental New Drug Application (sNDA) for this indication. Biomarker data analysis revealed that the MHC-II antigen presentation pathway played a key role in immunotherapy-chemotherapy combination. Higher gene expression of this pathway was significantly associated with longer progression-free survival (HR, 0.41; 95% CI, 0.23-0.76; P=0.0041) and could potentially serve as a predictive biomarker to select patients who can benefit from this regimen.

Professor Li ZHANG, Head of Department of Internal Medicine, Sun Yat-sen University Cancer Center, the primary investigator of the ORIENT-11 trial, stated: "Sintilimab in combination with pemetrexed and platinum chemotherapy showed improved efficacy and no new safety signals in locally advanced or metastatic nonsquamous NSCLC. These results will further our understanding of the performance of this combination in certain types of patients."

Dr. Wei XU, Vice President of New Drug Biology and Translational Medicine of Innovent, stated: "We were very pleased to release these biomarker results at the ESMO (Free ESMO Whitepaper) Virtual Congress 2020. MHC-II antigen presentation pathway might predict clinical efficacy of immunotherapy-chemotherapy. This finding could improve our understanding of the mechanism of action of this combination and provide a scientific rationale for future selection of patients who could benefit most."

Dr. Li WANG, Senior VP of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated: "Biomarker exploration is very important to advance cancer immunotherapy. We are very pleased that our discovery of a potential biomarker for immunotherapy will be shared at ESMO (Free ESMO Whitepaper). I would like to thank all the investigators, scientists and patients involved in the trial."

About ORIENT-11 Trial

ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating the efficacy and safety of TYVYT (sintilimab injection) or placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy as a first-line treatment for advanced or recurrent nonsquamous non-small cell lung cancer (nsqNSCLC) without sensitizing EGFR mutations or ALK rearrangements (ClinicalTrials.gov, NCT03607539). The primary endpoint is progression-free survival (PFS) assessed by Independent Radiographic Review Committee based on RECIST v1.1. The key secondary endpoints include overall survival (OS) and safety profile.

A total of 397 subjects have been enrolled in the ORIENT-11 trial and randomized in a 2:1 ratio to receive either TYVYT (sintilimab injection) 200mg or placebo in combination with ALIMTA (pemetrexed) and platinum chemotherapy every three weeks for up to four cycles, followed by either TYVYT (sintilimab injection) or placebo plus ALIMTA (pemetrexed) maintenance therapy. The subjects will receive treatment until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation. Conditional crossover is permitted.

About nsqNSCLC

Lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of NSCLC is locally advanced or metastatic at initial diagnosis, resulting in patients with having little to no chance of radical resection. Meanwhile, even after radical surgery, patients have a high chance of recurrence and eventually die from disease progression. About 70 percent of NSCLC in China is nonsquamous subtype and 50 percent of nsqNSCLC is without sensitizing EGFR mutations or ALK rearrangements. These patients do not respond well to targeted therapy and there are limited treatment options available to them.

About TYVYT (Sintilimab Injection)

TYVYT (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Lilly, has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL) in November 2019. In April 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum chemotherapy as first-line therapy in nonsquamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT (sintilimab injection) monotherapy met the primary endpoint in the ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma. In August 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with GEMZAR (gemcitabine for injection) and platinum chemotherapy as first-line therapy in squamous NSCLC.

TYVYT (sintilimab injection) is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies for TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. Meanwhile, Innovent is conducting clinical research studies on TYVYT (sintilimab injection) worldwide.

On September 20, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported interim results from the CHRYSALIS study (NCT02609776) evaluating amivantamab, a fully human bispecific antibody that targets epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (MET) mutations,1 in combination with the third-generation EGFR tyrosine kinase inhibitor (TKI) lazertinib2 in patients with non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R mutations.3 Investigators assessed efficacy using overall response rate (ORR) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1), clinical benefit rate, duration of response and the safety profile of amivantamab and lazertinib, in the 91 patients treated with the combination across dose escalation and expansion cohorts (Press release, Johnson & Johnson, SEP 20, 2020, View Source [SID1234565393]).3 The study results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 (Abstract #1258O) as an oral presentation.3 Results from the CHRYSALIS study have led to new studies to further evaluate the potential of amivantamab and lazertinib combination therapy.4

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The CHRYSALIS study is an open-label, global, multicentre study evaluating the safety, pharmacokinetics and efficacy of amivantamab as a monotherapy and in combination with lazertinib in adult patients with advanced NSCLC.5 Exon 19 deletion and L858R mutations are common, accounting for 85 percent of all EGFR mutations in NSCLC.6 In the study, 91 patients with NSCLC harbouring EGFR exon 19 deletion or L858R mutations received the combination of amivantamab intravenously and lazertinib orally.3 The study enrolled 26 patients in dose escalation and identified a combination dose that was equivalent to monotherapy doses of both products.3 Additionally, 20 treatment-naïve patients with EGFR-mutated NSCLC were enrolled to further examine the safety, efficacy and tolerability in the first-line setting and 45 patients who had relapsed on osimertinib but were chemotherapy-naïve were enrolled to examine safety and efficacy in the resistance setting.3

In the treatment-naïve group, 20 patients receiving the combination of amivantamab and lazertinib achieved a 100 percent ORR (95 percent CI, 83 – 100).3 The median follow-up and treatment duration at the time of data cut-off was seven months (range 4 – 10).3 Among 45 osimertinib-relapsed, chemotherapy-naïve patients, the combination of amivantamab and lazertinib resulted in a 36 percent ORR (95 percent CI, 22 – 51), with one complete response and 15 partial responses.3 The clinical benefit rate for these patients was 60 percent (95 percent CI, 44 – 74).3 Biomarker and central nervous system analyses and efficacy by mechanism of osimertinib resistance are ongoing and will be presented at a future medical meeting.3

"Despite treatment advancements, lung cancer remains the leading cause of cancer deaths globally, and there are opportunities to improve treatment options for patients with non-small cell lung cancer with genetic factors such as EGFR mutations," said Byoung Chul Cho, M.D., Ph.D., Yonsei Cancer Centre, Yonsei University College of Medicine in Seoul, South Korea, and lead study investigator. "We are encouraged by these results that suggest amivantamab in combination with lazertinib may be a promising option in this specific disease cohort where a high unmet need remains for more targeted treatment options."

For the 91 treated patients, the majority of treatment-related adverse events (AEs) experienced were Grade 1-2.3 A low incidence of Grade ≥3 treatment-related AEs occurred, which included rash (four percent), hypoalbuminemia (two percent), increased gamma glutamyltransferase (one percent), hyponatraemia (one percent) paronychia (one percent) and interstitial lung disease (one percent).3 Related AEs leading to treatment discontinuation occurred in six percent of patients.3 Infusion-related reaction occurred predominantly at first infusion and did not impact subsequent dosing.3

The results from the CHRYSALIS study have led to new studies to further evaluate the potential of amivantamab and lazertinib combination therapy. The Phase 3 MARIPOSA study (NCT04487080) will assess the amivantamab and lazertinib combination versus osimertinib in previously untreated advanced EGFR-mutated NSCLC,4 and a Phase 1 trial (NCT04077463) has been initiated to examine the combination in patients who have progressed after treatment with osimertinib and chemotherapy.7

"Lung cancer is the biggest cause of cancer death in Europe and has one of the lowest five-year survival rates for cancer patients. At Janssen, we are committed to developing innovative targeted therapies that address the unmet needs for specific types of lung cancer, such as those with EGFR-mutated non-small cell lung cancer," said Joaquín Casariego, M.D., Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag, S.A. "The interim data from the evaluation of amivantamab and lazertinib in combination demonstrate encouraging potential for providing new treatment options for the advanced NSCLC patient population."

About Amivantamab

Amivantamab, formerly JNJ-61186372, is an investigational EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations and MET mutations and amplifications.3,5 In March 2020, amivantamab received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.8 These results were also presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Scientific Program.9 The production and development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody technology platform.10

About Lazertinib

Lazertinib is an oral, third-generation, brain-penetrant, EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR.11 Interim safety and efficacy results from the lazertinib Phase 1-2 study were published in The Lancet Oncology in 2019.2 In 2018, Janssen Biotech, Inc. entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.12

About Non-Small Cell Lung Cancer (NSCLC)

In Europe, it is estimated that over 470,000 patients were diagnosed with lung cancer in 2018, with around 85 percent diagnosed with NSCLC.13,14 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.13 The five-year survival rate for patients with metastatic NSCLC is currently 24 percent.15

The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.16 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase that helps cells grow and divide.16 EGFR mutations are present in 10 to 15 percent of Caucasian patients with NSCLC and occur in 40 to 50 percent of Asian patients who have NSCLC adenocarcinoma.17,18,19

On September 20, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported results from the ongoing ARROW clinical trial showing durable responses and a well-tolerated safety profile for GAVRETO (pralsetinib) in patients with advanced RET-mutant medullary thyroid cancer (MTC) (Press release, Blueprint Medicines, SEP 20, 2020, View Source [SID1234565391]). In these registrational data, GAVRETO demonstrated consistent clinical activity in patients across lines of therapy and regardless of RET mutation genotypes, including a high response rate in patients with gatekeeper mutations resistant to multi-kinase inhibitors. The results are being presented today in a proffered paper session during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020.

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"For patients with RET-mutant medullary thyroid cancer, there is an important need for targeted therapies like pralsetinib (GAVRETO) that are highly active across RET genotypes, including gatekeeper resistance mutations," said Mimi Hu, M.D., professor in the Department of Endocrine Neoplasia and Hormonal Disorders at The University of Texas MD Anderson Cancer Center. "The reported data highlight the robust clinical activity and safety of GAVRETO, with most patients remaining on treatment for prolonged periods of time. These results are a promising advancement for RET-mutant medullary thyroid cancer across both systemic treatment-naïve and previously treated patients."

"By selectively inhibiting RET alterations, GAVRETO has broad potential to address the limitations of multi-kinase inhibitors and enable transformative outcomes for patients with RET-mutant medullary thyroid cancer," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "Across first-line and previously treated settings, GAVRETO has shown durable clinical benefits and a well-tolerated safety profile that has remained consistent over time. With the recent FDA approval of GAVRETO in patients with RET fusion-positive metastatic non-small cell lung cancer, these data further support our efforts to bring this once-daily treatment to patients across multiple RET-driven tumor types."

As previously announced, the U.S. Food and Drug Administration (FDA) has accepted a new drug application (NDA) for GAVRETO for the treatment of patients with advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer. This NDA was accepted for priority review under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

In addition, Blueprint Medicines reported that the National Comprehensive Cancer Network has updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) to include GAVRETO as a preferred treatment option (category 2A) for patients with RET fusion-positive NSCLC as a first-line or subsequent therapy. This rating indicates that there is uniform NCCN consensus that the intervention is appropriate. The NCCN Guidelines are the recognized clinical standard for cancer care by U.S. healthcare providers and payers, and are maintained by a committee of expert physicians from leading U.S. cancer centers.

GAVRETO is being jointly commercialized by Genentech, a wholly owned member of the Roche Group, and Blueprint Medicines in the U.S. and will be commercialized by Roche outside of the U.S., excluding Greater China (Mainland China, Hong Kong, Macau and Taiwan).

Highlights from the ARROW Trial in Patients with RET-Mutant MTC

The presented data included response-evaluable patients with RET-mutant MTC who were previously treated with cabozantinib or vandetanib, or naïve to systemic treatment. Tumor response was assessed by blinded, independent central review using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. All patients received a GAVRETO starting dose of 400 mg once daily (QD), and results were reported as of a data cutoff date of February 13, 2020.

GAVRETO demonstrated broad clinical activity in patients with RET-mutant MTC with or without prior systemic therapy. In 53 patients previously treated with cabozantinib or vandetanib, the overall response rate (ORR) was 60 percent (95% CI: 46%, 74%) with one response pending confirmation, and the disease control rate (DCR) was 96 percent (95% CI: 87%, 100%). The median duration of response (DOR) was not reached (95% CI: not reached, not reached), with 94 percent of responders remaining on treatment. The median progression-free survival (PFS) was not reached (95% CI: not reached, not reached) in patients previously treated with cabozantinib or vandetanib.

In 19 systemic treatment-naïve patients who were ineligible for standard therapy per the study protocol, the confirmed ORR was 74 percent (95% CI: 49%, 91%), and the DCR was 100 percent (95% CI: 82%, 100%). The median DOR was not reached (95% CI: 7 months, not reached), with 93 percent of responders remaining on treatment. The median PFS was not reached (95% CI: not reached, not reached) in systemic treatment-naïve patients.

Five of six patients whose tumors had a RET V804M or V804L gatekeeper mutation achieved a clinical response. Three patients previously treated with multi-kinase inhibitors had a RET M918T activating mutation and a RET V804M or V804L gatekeeper resistance mutation at baseline, and all three of these patients had a clinical response following GAVRETO treatment.

The reported safety data included a total of 438 patients enrolled in the ARROW trial at a GAVRETO starting dose of 400 mg QD, regardless of tumor type. GAVRETO was well-tolerated with safety results consistent with previously reported data. Overall, treatment-related adverse events (AEs) were primarily Grade 1 or 2. The most common treatment-related AEs reported by investigators (≥15 percent) were increased aspartate aminotransferase, anemia, increased alanine aminotransferase, hypertension, constipation, decreased white blood cell count, neutropenia, decreased neutrophil count and hyperphosphatemia. Investigator-reported Grade 3 or higher treatment-related AEs (≥5 percent) were hypertension, neutropenia, anemia and decreased neutrophil count. Four percent of patients discontinued GAVRETO due to treatment-related AEs.

These data for GAVRETO are being reported in a proffered paper (Abstract Number: 1913O) at the ESMO (Free ESMO Whitepaper) Virtual Congress 2020. A copy of the data presentation is available in the "Science—Publications and Presentations" section of Blueprint Medicines’ website at www.BlueprintMedicines.com.

About RET-Altered Solid Tumors

RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and multiple types of thyroid cancer. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET fusions are observed at low frequencies in colorectal, breast, pancreatic and other cancers, as well as in patients with treatment-resistant EGFR-mutant NSCLC.

About the ARROW Trial

The Phase 1/2 ARROW trial (ClinicalTrials.gov Identifier: NCT03037385) is designed to evaluate the safety, tolerability and efficacy of GAVRETO in adults with RET-altered cancers. The trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in patients treated at 400 mg QD. The study’s objectives include assessing response, pharmacokinetics, pharmacodynamics and safety. The trial is enrolling patients at multiple sites in the United States, European Union and Asia.

Patients and physicians interested in the ARROW trial can contact the Blueprint Medicines study director at [email protected] or 1-888-BLU-PRNT (1-888-258-7768) in the U.S., or [email protected] or +31 85 064 4001 in Europe. Additional information is available at www.BlueprintClinicalTrials.com/ARROW and www.clinicaltrials.gov.

About GAVRETO (pralsetinib)

GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the FDA for the treatment of adults with metastatic RET fusion-positive NSCLC as detected by an FDA approved test. It is designed to selectively and potently target oncogenic RET alterations. In pre-clinical studies, GAVRETO inhibited RET at lower concentrations than other pharmacologically relevant kinases, including VEGFR2, FGFR2 and JAK2. For more information, visit GAVRETO.com.

GAVRETO is not approved for the treatment of any other indication in the U.S. by the FDA or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines and Roche are co-developing GAVRETO globally (excluding Greater China) for the treatment of patients with RET-altered NSCLC, various types of thyroid cancer and other solid tumors. The FDA has accepted an NDA for GAVRETO for the treatment of RET-mutant MTC and RET fusion-positive thyroid cancer, and the European Medicines Agency has validated a marketing authorization application for GAVRETO for the treatment of RET fusion-positive NSCLC. The FDA has granted breakthrough therapy designation to GAVRETO for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of GAVRETO in Greater China.