On June 2, 2018 NantWorks, LLC reported that its affiliate companies, NantHealth, Inc., (NASDAQ: NH), a leading next-generation, evidence-based, personalized healthcare company and NantOmics, LLC, the leader in molecular analysis and a member of the NantWorks ecosystem of companies, will present findings on how 17 percent of next generation sequencing (NGS) 50 gene panel variants are not expressed in RNA sequencing during the tumor biology session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting, an event bringing together 30,000 oncology professionals from June 1-5, 2018 at McCormick Place in Chicago, Illinois (Press release, NantHealth, JUN 2, 2018, View Source;p=RssLanding&cat=news&id=2352873 [SID1234527096]). NantWorks will be exhibiting at booth #7147 during the event.

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"By determining the frequency of non-expressed variants that would be tested by a standard NGS panel, our data shows that the identification of these genes can yield improved testing algorithms and treatment strategies," said Patrick Soon-Shiong, MD, founder of NantWorks. "We’re excited to share this data and look forward to further exploring how NGS can be used for target therapy in oncology."

Presentation Details

Seventeen percent of NGS 50 gene panel variants are not expressed in RNAseq, Abstract #12118
WHO: NantHealth, LLC and NantOmics, LLC
WHAT: Tumor Biology Session
WHEN: June 4, 1:15-4:45 PM CST
WHERE: Hall A, McCormick Place

Presentation Summary

This study analyzed the frequency of non-expressed variants that would be tested by a standard NGS panel through retrospective analysis of a database from a commercial DNA tumor: normal and RNAseq platform. In the 992 samples that were identified with paired DNA (WGS or WES) / RNAseq NGS, a total of 225,727 SNVs were detected. Across 37 tumor types the range of expression was 57% (melanoma) – 100% (uterine). In this analysis, 17 percent of detected variants were not expressed in the RNA sequence. As a result, the lack of RNA expression may contribute to less than expected clinical benefit with molecularly targeted therapies. Since the distribution is non-uniform, identification of these genes can yield improved testing algorithms and treatment strategies.

On June 2, 2018 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers, reported interim clinical data from the LOXO-292 global Phase 1 LIBRETTO-001 (LOXO-292 Investigated to Block RET-altered Tumors) dose escalation trial (Press release, Loxo Oncology, JUN 2, 2018, View Source [SID1234527090]). LOXO-292 is an investigational, highly potent and selective RET inhibitor. These data are being presented today at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (abstract 102).

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"The LOXO-292 Phase 1 data are striking," said Alexander Drilon, M.D., clinical director in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and presenting author. "The activity we reported is impressive and I am thrilled to see this promising efficacy with limited adverse events, especially in this heavily pre-treated patient population of RET fusion cancers, including those with brain metastases, and RET mutated MTC."

"We are very excited to share the initial LOXO-292 clinical experience with the oncology community at ASCO (Free ASCO Whitepaper)," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "We have long believed that patients with RET fusion cancers and RET mutated MTC needed a purpose-built medicine tailored to their tumors. We hope that LOXO-292 continues to deliver on that premise. Thank you to the patients, investigators and clinical trial teams who made possible today’s presentation."

Trial Background

The LIBRETTO-001 Phase 1 trial contains a dose escalation phase and a dose expansion phase. The dose escalation phase follows a "3+3" design. LOXO-292 is dosed orally in 28-day cycles. As dose cohorts are cleared, additional patients can enroll in these cleared cohorts. Intra-patient dose escalation is also permitted as dose cohorts are cleared. The primary endpoint of the trial is the determination of the maximum tolerated dose (MTD) or recommended dose for further study. Secondary endpoints include safety, overall response rate (by RECIST 1.1) and duration of response. The dose expansion phase is designed to further characterize the overall response rate, durability of response, and safety of LOXO-292 in predefined groups of patients with activating RET alterations.

Key Data Presented at ASCO (Free ASCO Whitepaper)

The data presented at ASCO (Free ASCO Whitepaper) were based on an April 2, 2018 data cut-off date. Eighty-two total patients had been enrolled to eight dose escalation cohorts: 20 mg QD (n=6), 20 mg BID (n=10), 40 mg BID (n=16), 60 mg BID (n=10), 80 mg BID (n=18), 120 mg BID (n=4), 160 mg BID (n=12) and 240 mg BID (n=6). RET alterations were identified by local laboratories either in tumor or plasma and included the following primary diagnoses:

38 patients with RET fusion-positive non-small cell lung cancer (NSCLC) (21 with prior MKI treatment, 17 without)
9 patients with RET fusion-positive thyroid cancer (8 with prior MKI treatment, 1 without)
2 patients with RET fusion-positive pancreatic cancer (1 with prior MKI treatment, 1 without)
29 patients with RET-mutated medullary thyroid cancer (MTC) (23 with prior MKI treatment, 6 without)
4 patients with no known activating RET alterations
In addition to many patients with prior MKI treatment, 46% of patients had received prior chemotherapy and 24% had received prior immunotherapy (47% of those with NSCLC).

Pharmacokinetic analyses during the dose escalation demonstrated dose-dependent increases in LOXO-292 exposure with increasing dose. Starting at the 40 mg BID dose and the 80 mg BID dose, respectively, LOXO-292 delivered sustained >IC90 RET fusion and >IC90 RET M918T-mutant target coverage, based on cell-based potencies.

The data presented at ASCO (Free ASCO Whitepaper), summarized below, are based on response assessments performed by each respective clinical trial site (local, investigator-assessed radiology).

1. Patients eligible for response evaluation include thyroid cancer (n=7), pancreatic cancer (n=2).
2. Excludes patients recently enrolled that remain on treatment, but have not had a first post-baseline response assessment.
3. Response status per RECIST 1.1. Overall response rate = CR+uCR+PR+uPR. Overall response rate, Confirmed overall response rate: all RET fusion-positive (30/39, 25/34), RET fusion-positive NSCLC (23/30, 20/27), RET fusion-positive other (7/9, 5/7), RET-mutant MTC (10/22, 6/18).
4. Excludes patients with unconfirmed CR/PR pending confirmation at time of data cut-off.
5. Unconfirmed responses in patients that remain on treatment awaiting a confirmatory response assessment.
6. Patients that discontinued treatment prior to a first post-baseline response assessment.

Anti-tumor activity was observed regardless of RET fusion partner (including KIF5B), RET mutation (including M918T and V804M gatekeeper mutations), and prior MKI treatment. Twelve patients with RET fusion cancers had central nervous system (CNS) metastases at enrollment and all remained on study without progression. Three of these patients had RECIST target lesions in the CNS, and all three exhibited intracranial partial responses. In patients with RET-mutant MTC, LOXO-292 treatment resulted in significant reductions in the serum tumor markers calcitonin and carcinoembryonic antigen (CEA).

As of the data cutoff, LOXO-292 demonstrated early evidence of durable activity, with 90% of RET fusion-positive cancer patients and 93% of RET-mutant MTC patients remaining on therapy. All responding patients across all tumor types remained on therapy. The longest responding patient on therapy was the first RET fusion-positive NSCLC patient enrolled, who had been on therapy for more than ten months as of the data cut-off date.

Most treatment-emergent adverse events were Grade 1 in severity. The treatment-emergent adverse events observed in ≥10% of patients, regardless of relationship to LOXO-292, were fatigue (12% Grade 1, 7% Grade 2, 0% ≥Grade 3), diarrhea (10% Grade 1, 6% Grade 2, 0% ≥Grade 3), constipation (13% Grade 1, 1% Grade 2, 0% ≥Grade 3), dry mouth (12% Grade 1, 0% ≥Grade 2), nausea (9% Grade 1, 4% Grade 2, 0% ≥Grade 3), and dyspnea (7% Grade 1, 2% Grade 2, 1% ≥Grade 3). Only two adverse events ≥Grade 3 were attributed to LOXO-292 (Grade 3 tumor lysis syndrome, Grade 3 increased ALT). An MTD had not been reached. At the 240 mg BID dose level, one dose limiting toxicity (DLT) was reported (aforementioned Grade 3 tumor lysis syndrome).

LOXO-292 also demonstrated robust reduction and clearance of RET alterations as detected in patients’ plasma cell free DNA (cfDNA). These data will be presented in a separate poster presentation on June 3, 2018.

LIBRETTO-001 Trial Update

The expansion cohorts of the LIBRETTO-001 trial are now open and enrolling at the 160 mg BID dose. This dose was selected for initial expansion based on its promising activity and tolerability profile. Additional dose exploration above 160 mg BID is ongoing and patients enrolled to the expansion cohorts may dose escalate should a higher dose be advanced.

About the ASCO (Free ASCO Whitepaper) Presentations

LOXO-292 data are being presented in two presentations at ASCO (Free ASCO Whitepaper):

"A phase 1 study of LOXO-292, a potent and highly selective RET inhibitor, in patients with RET-altered cancers." This abstract is being presented in an oral presentation by Dr. Alexander Drilon, Memorial Sloan Kettering Cancer Center, during a Clinical Science Symposium session entitled, "Tumor Genomics: Finding the Target, Hitting the Target" from 8:00 – 9:30AM CT on Saturday, June 2, 2018 (Abstract 102).
"Detection and clearance of RET variants in plasma cell free DNA (cfDNA) from patients (pts) treated with LOXO-292." This abstract is being presented as a poster by Dr. Geoff Oxnard, Dana Farber Cancer Institute, during the Lung Cancer—Non-Small Cell Metastatic poster session from 8:00 – 11:30AM CT on Sunday, June 3, 2018 (Abstract 9048).
The presentations will be available online at View Source at the time of their scheduled presentation at ASCO (Free ASCO Whitepaper).

Conference Call and Webcast Information
Loxo Oncology management will host a conference call and live webcast with slides and Q&A today at 4:00 p.m. CT to discuss the LOXO-292 data. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 3597058. A live webcast of the presentation will be available at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the company’s website for 30 days following the call.

On June 2, 2018 Jounce Therapeutics, Inc. (NASDAQ:JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that its preliminary data from its ongoing Phase 1/2 ICONIC trial, an adaptive design, open-label trial evaluating JTX-2011 alone and in combination with nivolumab in patients with advanced solid tumors (Press release, Jounce Therapeutics, JUN 2, 2018, View Source;p=RssLanding&cat=news&id=2352867 [SID1234527089]). Safety and preliminary clinical activity data from all evaluable patients across multiple tumor types will be presented in an oral presentation today, Saturday, June 2, 2018 at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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"We are encouraged by the early signal of clinical activity in heavily pre-treated patients, accompanied by an ICOS pharmacodynamic biomarker. We believe that this biomarker may help guide further development of JTX-2011," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Importantly, JTX-2011 continues to be safe and well-tolerated both as a single agent and in combination with nivolumab. We look forward to continuing clinical evaluation of JTX-2011, including initiation of new combination dose escalation cohorts within the ICONIC trial of JTX-2011."

The ICONIC study (ICOS AgONist Antibody for Immunotherapy in Cancer Patients) is an open label, dose escalation and expansion clinical study of JTX-2011 alone and in combination with a fixed dose of nivolumab in patients with advanced solid tumors. Patients were heavily pre-treated with approximately 65 percent having received 3 or more prior therapies (i.e. 4th line or greater); approximately 65 percent discontinued during the first three cycles. The adaptive design includes Parts A and B (Phase 1), and C and D (Phase 2), with the Phase 2 cohorts enriched for high ICOS expression. The data presented today include preliminary efficacy data from all evaluable patients as of an April 4, 2018 cut-off date. The Phase 1 portion of ICONIC was a dose escalation study to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). The patients in Phase 2 received JTX-2011 0.3 mg/kg every 3 weeks alone or in combination with nivolumab 240 mg every 3 weeks. Preliminary efficacy evaluation included tumor reductions and RECIST (response evaluation criteria in solid tumors) responses.

Summary of JTX-2011 ICONIC Data

Safety

JTX-2011 was well tolerated alone and in combination with nivolumab 240 mg every 3 weeks. The overall safety profile observed was consistent with previously reported data from the Phase 1 portion of the ICONIC trial.
Clinical Activity

Gastric Cancer

A RECIST partial response (PR) with JTX-2011 monotherapy was observed in 1 of 8 Phase 2 patients (7 PD-1 inhibitor naïve, including PR), ongoing at 8.5+ months.
Two RECIST PRs with JTX-2011 plus nivolumab were observed in 1 of 4 Phase 1 patients (all PD-1 inhibitor naïve) and 1 of 28 Phase 2 patients (22 PD-1 inhibitor naïve, including PR), ongoing at 11+ and 4+ months, respectively.
Disease control(1) was observed in 10 of 28 and tumor reductions were observed in 8 of 28 Phase 2 patients treated with JTX-2011 plus nivolumab, including both PD-1 inhibitor naïve and PD-1 inhibitor failures.
Triple Negative Breast Cancer (TNBC)

A RECIST PR with JTX-2011 plus nivolumab was observed in 1 of 17 Phase 2 patients (16 PD-1 inhibitor naïve, including PR), ongoing at 4+ months.
Disease control was observed in 3 of 17 and tumor reductions were observed in 2 of 17 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor naïve.
Head and neck squamous cell cancer (HNSCC) PD-1 inhibitor failures

Disease control was observed in 2 of 16 and tumor reductions were observed in 1 of 16 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor failures, of whom over 50 percent were refractory(2) to prior PD-1 inhibitors.
Non-small cell lung cancer (NSCLC) PD-1 inhibitor failures

Disease control was observed in 7 of 12 and tumor reductions were observed in 4 of 12 Phase 2 patients treated with JTX-2011 plus nivolumab, all PD-1 inhibitor failures.
(1) Disease control= confirmed PR + SD ≥ 9 weeks
(2) Refractory= best response to prior PD-1 inhibitor was progressive disease

Biomarkers

In a preliminary analysis of evaluable fresh pre-treatment biopsies, rates of disease control and tumor reduction appear higher in subjects with high ICOS scores.
An ICOS pharmacodynamic biomarker (emergence of peripheral blood ICOS high CD4 T cell population) appears to associate with anti-tumor activity.
Present in 7 of 7 subjects with target lesion PRs
Absent in 10 of 10 subjects with progressive disease
Based on preliminary signals of clinical activity associated with an ICOS pharmacodynamic biomarker, Jounce is advancing clinical evaluation of JTX-2011. The next steps for the program include continuing to evaluate the ongoing data and the initiation of two new dose escalation cohorts within the ICONIC trial of JTX-2011, one in combination with ipilimumab and one in combination with pembrolizumab. The new ipilimumab combination cohort may enable Jounce to explore a new combination mechanism that is supported by clinical and pre-clinical research. Exploration with pembrolizumab at its approved q3w dose and schedule may allow the Company to evaluate JTX-2011in combination with a PD-1 inhibitor in earlier lines of therapy.

"We look forward to evaluating the new additional combinations with JTX-2011. From our founding science, the platform we have built, and the team we have in place, we believe we are well positioned to optimize the development of JTX-2011," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "We are grateful to all of the patients who have participated in our trial, their families, our investigators and their study teams. This was a complex biomarker heavy trial that was well executed by the Jounce team."

ICONIC Enrollment Status
Phase 1 has completed enrollment and Phase 2 is nearing completion of enrollment. Given the pace of enrollment of the combination cohorts in gastric cancer, TNBC, HNSCC, NSCLC and the overall quantity of the data collected, Jounce made the decision to stop recruitment of other solid tumors and of the more slowly enrolling monotherapy and melanoma combination cohorts.

Jounce Therapeutics to Host Event and Webcast
Jounce Therapeutics will host an investor and analyst event beginning at 6:30 p.m. CT (7:30 p.m. ET) with a live webcasted presentation beginning at 7:00 p.m. CT (8:00 p.m. ET), on Monday, June 4, 2018. To access the live webcast, please visit the "Events & Presentations" page in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.

About JTX-2011
Jounce’s lead product candidate, JTX-2011, is a monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO­Stimulator, a protein on the surface of certain T cells. Preclinical data support that JTX-2011 may have a dual mechanism of action that stimulates anti-tumor T effector cells, and also reduces the immunosuppressive T regulatory cells in the tumor microenvironment. The company is developing JTX-2011 to treat solid tumors as a single agent and in combination with other therapies.

On June 2, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that results from the Phase III IMpower131 study showed Tecentriq (atezolizumab) plus chemotherapy (carboplatin and Abraxane [albumin-bound paclitaxel; nab-paclitaxel]) reduced the risk of disease worsening or death (progression-free survival; PFS) by 29 percent compared with chemotherapy (carboplatin and nab-paclitaxel) alone in the initial (first-line) treatment of people with advanced squamous non-small cell lung cancer (NSCLC) (median PFS=6.3 vs. 5.6 months; hazard ratio [HR]=0.71, 95% CI: 0.60, 0.85, p=0.0001) (Press release, Hoffmann-La Roche, JUN 2, 2018, View Source [SID1234527077]).1 The 12-month PFS rate was doubled for people who received the Tecentriq combination (24.7 percent) compared to those who received chemotherapy alone (12.0 percent). A statistically significant overall survival (OS) benefit was not observed at the interim analysis, and the study will continue as planned. The safety profile of the Tecentriq plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.

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"The IMpower131 data further inform our understanding of this difficult-to-treat type of lung cancer and will continue to as we evaluate additional outcomes from this study," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "IMpower131 is one of eight Phase III trials from our extensive research programme evaluating Tecentriq alone or in combination with other medicines in different types of lung cancer."

Data will be featured in the official American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting press programme on Saturday, 2 June, 2018, at 08:00 am CDT. The oral data presentation will be on Monday, 4 June, 2018, at 15:00–15:12 pm CDT (Abstract LBA9000).

About the IMpower131 study
IMpower131 is a Phase III, open-label, multicentre, randomised study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and nab-paclitaxel or Tecentriq in combination with carboplatin and paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone in people with stage IV squamous-cell NSCLC who have not been previously treated with chemotherapy. The study enrolled 1,021 people who were randomised equally (1:1:1) to receive:

Tecentriq plus carboplatin and paclitaxel (Arm A), or
Tecentriq plus carboplatin and nab-paclitaxel (Arm B), or
Carboplatin and nab-paclitaxel (Arm C, control arm)
During the treatment-induction phase, people in Arm A received four or six cycles of Tecentriq plus carboplatin and paclitaxel, given on day one of each 21-day cycle. This was followed by maintenance therapy with Tecentriq every three weeks until progression of the cancer, or for as long as clinical benefit was observed.

During the treatment-induction phase, people in Arm B received four or six cycles of Tecentriq, carboplatin and nab-paclitaxel. Tecentriq and carboplatin were administered on day one of each 21-day cycle. Nab-paclitaxel was administered on days one, eight and 15 of each 21-day cycle. This was followed by maintenance therapy with Tecentriq every three weeks until progression of the cancer, or for as long as clinical benefit was observed.

During the treatment-induction phase, people in Arm C received four or six cycles of carboplatin and nab-paclitaxel. Carboplatin was administered on day one of each 21-day cycle, and nab-paclitaxel was administered on days one, eight and 15 of each 21-day cycle. In the maintenance phase, participants received best supportive care.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the intention-to-treat (ITT) population (Arm B vs. Arm C)
OS in the ITT population (Arm B vs. Arm C)
Key secondary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the Tumour Cell (TC) 2/3 or Tumour-Infiltrating Immune Cell (IC) 2/3 population
PFS as determined by the investigator using RECIST v1.1 in the TC1/2/3 or IC1/2/3 population
OS in the TC2/3 or IC2/3 population
OS in the TC1/2/3 or IC1/2/3 population
Percentage of participants with objective response (OR) as determined by the investigator using RECIST v1.1 in the ITT population
Duration of response (DoR) as determined by the investigator using RECIST v1.1 in the ITT population
IMpower131 met its PFS co-primary endpoint per study protocol. This analysis of IMpower131 evaluated Arm B vs. Arm C. Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet. As per the statistical analysis plan, Arm B (Tecentriq plus carboplatin and nab-paclitaxel) must demonstrate a statistically significant OS result vs. Arm C (carboplatin and nab-paclitaxel), before an analysis between Arm A (Tecentriq plus carboplatin and paclitaxel) and Arm C can be made for PFS and OS.

A summary of the IMpower131 results are included below:

The safety profile of the Tecentriq plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events related to treatment were observed in 20 percent of people who received Tecentriq plus chemotherapy compared to 10 percent of those who received chemotherapy alone.

About NSCLC
Lung cancer is the leading cause of cancer death globally.2 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.3 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.3 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. The squamous form tends to grow near the centre of the lung, and accounts for approximately 25-30% of all NSCLC cases.4

About Tecentriq (atezolizumab)
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 Q 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.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

Abraxane is a registered trademark of Abraxis Bioscience, LLC, a wholly owned subsidiary of Celgene Corporation.

On June 2, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported the presentation today of updated data from its ongoing Phase 1 clinical trial of DCC-2618, the company’s broad-spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2018, in Chicago, Illinois and provided additional clinical and regulatory updates on DCC-2618 (Press release, Deciphera Pharmaceuticals, JUN 2, 2018, View Source [SID1234527070]).

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Suzanne George, M.D. Assistant Professor of Medicine, Harvard Medical School and Clinical Director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute presented the poster titled "Mutational Profile of Drug Resistant GIST Patients Enrolled in the Phase 1 Study of DCC-2618". In addition to describing the mutational profile of KIT in GIST patients, the poster includes details of locally-read Objective Response Rates (ORR) and Disease Control Rates (DCR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) in second, third, and fourth and fourth line plus GIST patients that received DCC-2618 at doses of ≥100mg daily for at least one 28-day cycle prior to February 2, 2018:

The combined 24% ORR and 80% 3-month DCR in second and third line patients receiving DCC-2618 at doses of ≥100mg per day exceeds previously published results of registrational trials for the currently approved therapies for second line (sunitinib) and third line (regorafenib), which have reported ORRs of 7.0% and 4.5%, respectively, and levels of disease control of 60% and 53%, respectively.

"The preliminary data presented today on DCC-2618’s activity in second and third line GIST patients is very encouraging and supports the planned initiation later this year of our Phase 3 trial, INTRIGUE, in second line GIST patients," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "The mutational profiling data across second, third and fourth line GIST patients observed in the Phase 1 study also demonstrates the need for the broadest spectrum of KIT inhibition in all GIST patients who previously received imatinib."

"We are very pleased with the results presented today demonstrating DCC-2618’s potential to provide improved clinical benefit for not only heavily pre-treated patients, but also for second and third line GIST patients," said Oliver Rosen, M.D. Chief Medical Officer of Deciphera. "Combined with the tolerability data presented at AACR (Free AACR Whitepaper) in April 2018, these results demonstrate the potential of DCC-2618 as an effective and well tolerated therapy for a wide range of GIST patients."

Highlights from the poster presentation include:

Initial Objective Response Rates and Disease Control Rates with DCC-2618 at Doses of ≥100mg Daily in Second and Third Line GIST Patients Exceed Previously Published Results of Registrational Trials for Currently Approved Therapies, as well as the Results Observed in Heavily Pre-Treated GIST Patients Receiving DCC-2618:
24% ORR with DCC-2618 observed to date in second and third line GIST patients is higher than that reported for sunitinib in second line patients (7.0%) or regorafenib in third line patients (4.5%).
These interim results show improved ORR and 3-month DCR in second line GIST patients treated with DCC-2618 compared to fourth and fourth line plus GIST patients treated with DCC-2618.
Mutational Profiling Data Across Second, Third and Fourth Line GIST Patients Demonstrates the Breadth of KIT Mutations in GIST and the Ability of DCC-2618 to Reduce KIT Mutant Allele Frequency (MAF):
Resistance mutations in KIT in exons 13, 14, 17 and 18, or a combination thereof, occurs in second, third and, fourth and fourth line plus patients.
The KIT mutational profile in both tumors and plasma at baseline in GIST patient supports the need for a broad-spectrum KIT inhibitor in all post-imatinib lines of therapy.
57 of 73 patients (78%) receiving DCC-2618 at doses of ≥100 mg daily demonstrated reductions in KIT MAF of more than 50%.
In addition, the company is providing the following clinical and regulatory updates on DCC-2618:

Planned Initiation of a Phase 3 Trial in Second Line GIST Patients in 2018
Preliminary efficacy results in second line patients together with recently presented tolerability data at the recommended phase 2 dose (RP2D) of 150mg QD support the planned, randomized Phase 3 trial, INTRIGUE, in second line GIST.
Following discussions with regulatory authorities in the United States and in Europe, the company has designed INTRIGUE as a randomized, multicenter, open-label, Phase 3 trial in second line GIST. This registration study is expected to enroll approximately 350 patients who will be randomized 1:1 to either DCC-2618 or sunitinib, the current standard of care in second line; with median progression free survival as the primary endpoint.
Interim Results with DCC-2618 at Doses of ≥100mg Daily Demonstrate Robust Clinical Activity in Heavily Pretreated GIST Patients, Including Patients Previously Treated with the Investigational Agent avapritinib (BLU-285):
10 patients with KIT-driven GIST who previously received avapritinib were enrolled and treated with DCC-2618 as of January 31, 2018.
6 out of 10 (60%) of these patients achieved stable disease as best response by RECIST during treatment with DCC-2618. In addition, one patient achieved stable disease following intra-patient dose escalation to 150mg BID.
5 out of 10 (50%) of these patients were on study as of April 18, 2018.
3 out of 10 (30%) of these patients received DCC-2618 for more than six months. Two of these patients achieved continued stable disease and remain on study as of April 18, 2018. The third patient with progressive disease was dose escalated and was reported as off study as of April 18, 2018.
A copy of the poster presentation will be available on the Science section of the Deciphera website under "Presentations and Publications" at www.deciphera.com.

About DCC-2618

DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and glioblastoma multiforme. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is a KIT and PDGFRα inhibitor that blocks initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST as well as the primary D816V exon 17 mutation involved in SM. DCC-2618 also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST.