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Exact Sciences Presents New Stool-Based Colorectal Cancer Screening Performance Data, Initiates Prospective Screening Study

On October 29, 2019 Promising research from Exact Sciences Corp. and Mayo Clinic shows new methylation and protein markers detect colorectal cancer and advanced adenomas with high accuracy (Press release, Exact Sciences, OCT 29, 2019, View Source [SID1234549969]). Findings from the blinded, case-control study were presented at the American College of Gastroenterology’s (ACG) 2019 Annual Scientific Meeting today. The study is part of an effort to increase specificity of Cologuard, while maintaining its high level of sensitivity. Working in collaboration with Mayo Clinic, Exact Sciences has identified novel markers and improved laboratory processes to help achieve its performance enhancement goals and has initiated a 10,000-patient prospective study to validate the performance of the enhanced test.

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The new markers were tested alongside the current Cologuard markers on 725 stool samples, including 117 colorectal cancers (CRC), 120 advanced adenomas (AA), 161 non-advanced adenomas (non-AA), and 327 controls. Results showed 92% CRC sensitivity and 65% AA sensitivity at 92% specificity for the new markers. In this study, the new markers exceeded the specificity and sensitivity of the markers currently used in Cologuard.

Current markers * 87%
specificity

New markers

92% specificity

Difference

CRC sensitivity

88%

92%

+4%

AA sensitivity

53%

65%

+12%

Re-weighted AA sensitivity **

39%

46%

+7%

*Cologuard performance was established in DeeP-C, a prospective study of 10,000 average-risk, asymptomatic patients. The data displayed in this table show performance in a smaller case-control study of 725 samples.

**AA sensitivity re-weighted to match distribution by size of adenoma found in DeeP-C. AA sensitivity is expected to be lower in a prospective study.

"The data presented at ACG are promising," said Kevin Conroy, chairman and CEO of Exact Sciences. "This new study demonstrates the potential to make Cologuard, an accurate, convenient screening option, even better for patients and gives us confidence to move forward with a prospective study. We look forward to generating additional evidence, making an enhanced test available to patients, and solidifying Exact Sciences as the leader in the early, accurate detection of colorectal cancer."

To establish the sensitivity and specificity of the novel multi-target stool DNA test, Exact Sciences recently launched the BLUE-C study, a multi-center, prospective study, with the first patient expected to enroll this November. More than 10,000 patients 40 years of age and older and scheduled for a CRC screening colonoscopy will be enrolled. Patients will collect a stool sample and perform a commercially available fecal immunochemical test (FIT) prior to screening colonoscopy. Patients will be invited to provide a blood sample that Exact Sciences intends to use for validation of a potential blood-based screening test for CRC. Collecting stool and blood in one study is expected to provide significant cost and timing efficiencies.

Screening for CRC can help save lives by preventing the disease or detecting it early.1 Tests that can help accurately detect AAs and early-stage CRC provide the best chance of preventing or treating the disease before it progresses. CRC invades more layers of the colon wall and the blood supply as it advances, making it difficult for blood-based tests to accurately detect early-stage disease.2 Even with this biological limitation, blood-based tests could provide another option to get more people screened.

"While further studies will establish the clinical performance of these new markers, we are encouraged by the strong results presented today," said Paul Limburg, MD, MPH, AGAF, chief medical officer of Exact Sciences and gastroenterologist at Mayo Clinic. "The discovery of these markers by the Exact Sciences and Mayo Clinic teams is fueled by our spirit to continuously improve and advance the fight against this deadly disease."

About the BLUE-C study
The primary objective of this multi-center, prospective study is to determine the sensitivity and specificity of a novel multi-target stool DNA (mt-sDNA) screening test for CRC, using colonoscopy as the reference method. Lesions will be confirmed as malignant by histopathologic examination. Patients 40 years of age and older who are scheduled for a CRC screening colonoscopy will be eligible to participate. After providing written consent to participate in the study and before a screening colonoscopy, subjects will be provided with a stool collection kit and will collect a stool sample for the mt-sDNA screening test and for a commercially available FIT test. Subjects will undergo colonoscopy within approximately 60 days of enrollment. Subjects and clinicians will remain blinded to the results of the mt-sDNA CRC screening test and the FIT test, which will not be used in clinical management. Enrolled subjects will have the option to enroll in a blood collection sub-study for the development of a potential blood-based screening test for CRC.

DelMar Pharmaceuticals to Present Updates of Two Phase 2 Clinical Trials of VAL-083 at the 2019 Society for NeuroOncology Annual Meeting

On October 29, 2019 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported that two posters updating results from the company’s two Phase 2 clinical trials of VAL-083 will be presented at the 2019 Society for NeuroOncology Annual meeting in Phoenix, Ariz (Press release, DelMar Pharmaceuticals, OCT 29, 2019, View Source [SID1234549968]). Details regarding the posters are as follows:

Title: "Clinical Trial of VAL-083 in Newly-Diagnosed MGMT-unmethylated GBM: Half-Way Report"
Date/Time: Friday, November 22, 2019, 6:00 PM MT
Lead Author: Dr. Zhong-Ping Chen
This poster will include data from the company’s ongoing Phase 2 trial of VAL-083 being conducted at Sun Yat-sen University Cancer Center as a first line therapy, and includes updates on enrollment, safety and efficacy.

Title: "Phase 2 study of dianhydrogalactitol (VAL-083) in patients with MGMT-unmethylated, bevacizumab-naïve glioblastoma in the recurrent and adjuvant setting"
Date/Time: Friday, November 22, 2019, 6:00 PM MT
Lead Author: Dr. Barbara O’Brien
This poster will include data from the company’s ongoing Phase 2 trial of VAL-083 being conducted at M.D. Anderson Cancer Center as a treatment in the recurrent and adjuvant settings, and includes updates on enrollment, safety and efficacy.

The 2019 Society for NeuroOncology Annual meeting will be held from November 20-24, 2019 at the JW Marriott Desert Ridge, 5350 E. Marriott Drive in Phoenix, Ariz.

Deciphera Pharmaceuticals Presents Updated Data from Ripretinib and DCC-3014 Programs at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

On October 29, 2019 Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage biopharmaceutical company addressing key mechanisms of tumor drug resistance, reported the presentation of updated results from its ongoing Phase 1 study of ripretinib, a broad-spectrum KIT and PDGFRα inhibitor, in patients with second-line through fourth-line plus GIST, as well as its Phase 1 study of DCC-3014, an oral inhibitor of CSF1R, in patients with advanced solid tumors (Press release, Deciphera Pharmaceuticals, OCT 29, 2019, View Source [SID1234549967]). The data are being presented today at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston.

"These updated results continue to underscore the potential of our diverse pipeline of product candidates, all generated using our proprietary kinase switch control inhibitor platform, to improve the lives of cancer patients," said Matthew L. Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. "Of note, we believe ripretinib continues to demonstrate strong clinical benefit in post-imatinib GIST patients, particularly in the second-line setting. These results bolster our confidence in the ongoing INTRIGUE pivotal Phase 3 clinical study, which is designed to support potential regulatory approvals in patients with second-line GIST."

Ripretinib

Updated results from the Company’s ongoing Phase 1 study of ripretinib in patients with second-line through fourth-line plus GIST included data from 142 GIST patients receiving 150 mg of ripretinib once daily (QD) as the starting dose, which is the dose being utilized in the Company’s INVICTUS and INTRIGUE registration-enabling studies, as of an August 10, 2019 data cutoff date. The table below includes local, investigator-assessed objective response rate (ORR) by best response as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, median duration of response, median progression free survival (mPFS) and mean treatment duration.

Line of Therapy

2nd Line

(n=31)

3rd Line

(n=28)

≥4th Line

(n=83)

ORR (confirmed responses only)

19%

14%

Median Duration of Response

80 weeks

NE(1)

76 weeks

mPFS

46 weeks

36 weeks

24 weeks

Mean Treatment Duration(2)

56 weeks

58 weeks

45 weeks

(1) NE = not estimable; (2) Includes 64 patients who elected for intra-patient dose escalation from 150 mg QD to 150 mg twice daily (BID).

Data from GIST patients receiving ≥ 100 mg of ripretinib daily (n=178) in the ongoing Phase 1 study, as of an August 10, 2019 cutoff date, including 2nd line (n=37), 3rd line (n=31), and ≥4th line (n=110) patients were (a) ORR (confirmed responses only): 2nd line (22%), 3rd line (13%), ≥4th line (7%); (b) median duration of response: 2nd line (80 weeks), 3rd line (NE), ≥4th line (48 weeks); (c) mPFS: 2nd line (46 weeks), 3rd line (40 weeks), ≥4th line (24 weeks); (d) mean treatment duration (includes 72 patients who elected for intra-patient dose escalation to 150 mg BID): 2nd line (53 weeks), 3rd line (54 weeks), ≥4th line (48 weeks).

Ripretinib was generally well tolerated and the updated adverse events were consistent with previously presented Phase 1 data in patients with GIST. Grade 3 or 4 treatment-emergent adverse events (TEAEs) in >5% of patients were increase in lipase level (n=25; 18%), anemia (n=11; 8%), and abdominal pain (n=11; 8%).

DCC-3014

The Company’s Phase 1 study of DCC-3014 was designed to evaluate the safety, pharmacokinetics and pharmacodynamics of multiple doses of DCC-3014 in patients with advanced solid tumors. The Company expects to present preliminary data from initial tenosynovial giant cell tumor (TGCT) patients at the 2019 Connective Tissue Oncology Society (CTOS) Annual Meeting being held November 13-16 in Tokyo, Japan.

As of the data cut-off date of September 10, 2019, increasing doses of DCC-3014 were assessed in seven dose cohorts across 36 patients with advanced solid tumor tumors. This included one dose cohort that received 10 mg once daily and six dose cohorts that received a three to five day loading dose regimen at doses of up to 50 mg followed by a schedule of daily, once-weekly or twice-weekly maintenance dosing with DCC-3014.
Data demonstrated dose-proportional exposure for DCC-3014 and exposure to DCC-3014 was associated with an increase in plasma CSF1 and IL-34, rapid and sustained reduction of CD16+ monocytes in peripheral blood, and substantial decreases in CD163+ macrophages in tumor.
DCC-3014 was generally well-tolerated, with most treatment-emergent adverse events (TEAEs) Grade 1 or 2. Most common related TEAEs ≥10% were fatigue (n=6;17%), diarrhea (n=4; 11%), and nausea (n=4; 11%). Grade 3 or 4 related TEAEs occurred in 4 patients, which were grade 3 aspartate aminotransferase (AST) increase, grade 4 lipase increase, grade 3 amylase increase, and grade 3 colitis. Serious adverse events were reported in 17 patients; none of which were related to DCC-3014.
The dose escalation evaluation is ongoing to determine a recommended phase 2 dose for advanced solid tumors and diffuse-type TGCT.
A copy of each presentation is available at www.deciphera.com/science/presentation-publications/.

About Ripretinib

Ripretinib is an investigational tyrosine kinase switch control inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. Ripretinib is currently in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and other cancers. Ripretinib inhibits 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. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib. For more information about the Company’s clinical trials with ripretinib, please visit www.clinicaltrials.gov.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (MainlandChina, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.

About DCC-3014

DCC-3014 is an investigational, orally administered, potent and highly selective inhibitor of CSF1R. DCC-3014 was designed using the Company’s proprietary switch control kinase inhibitor platform to selectively bind to the CSF1R switch pocket. DCC-3014 has greater than 100-fold selectivity for CSF1R over other closely related kinases and has an even greater selectivity for CSF1R over approximately 300 other human kinases. CSF1R controls the differentiation and function of macrophages including Tumor Associated Macrophages (TAMs) whose density within certain tumors including cancers of the breast, cervix, pancreas, bladder and brain correlates with poor prognosis. Tumors induce TAMs to suppress a natural immune response mediated by cytotoxic T-cells, a type of lymphocyte that would otherwise eradicate the tumor; a process known as macrophage checkpoints. Through inhibition of CSF1R, DCC-3014 has in preclinical studies demonstrated potent macrophage checkpoint inhibition as both a single agent and in combination with PD1 inhibitors. DCC-3014 is currently being evaluated in a Phase 1 clinical study. For more information about the clinical trial design please visit www.clinicaltrials.gov (NCT03069469).

CytomX Therapeutics Announces Initiation of Phase 2 Clinical Trial Evaluating the Anti-PD-L1 Probody CX-072 in Combination with YERVOY® in Patients with Relapsed or Refractory Melanoma

On October 29, 2019 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported the initiation of the Phase 2 PROCLAIM (Probody Clinical Assessment In Man) CX-072-002 program evaluating the anti-PD-L1 Probody CX-072, in combination with the anti-CTLA-4 antibody, YERVOY (ipilimumab), in patients with relapsed or refractory melanoma (Press release, CytomX Therapeutics, OCT 29, 2019, View Source [SID1234549966]).

"The initiation of this first Phase 2 study for CX-072 marks the ongoing advancement of our innovative pipeline of Probody therapeutics and reflects our vision for this novel checkpoint inhibitor to become a differentiated centerpiece of combination therapies in multiple cancer types," said Sean McCarthy, D.Phil., president, chief executive officer and chairman of CytomX Therapeutics.

"Patients whose melanoma has progressed despite prior treatment with checkpoint inhibition remain a significant unmet medical need. This exciting study leverages our unique technology platform to enable a more powerful combination therapy directed against the two best validated pathways in immuno-oncology and could represent a significant advance in outcomes for these patients who have few treatment options," said Amy Peterson, M.D., chief development officer of CytomX Therapeutics.

About the PROCLAIM-CX-072-002 Ipilimumab Combination Study

PROCLAIM-CX-072-002 is an open-label, multi-center Phase 2 clinical study (NCT03993379) that allows for the testing of CX-072 in combination with ipilimumab in patients with unresectable or metastatic melanoma whose disease has progressed or relapsed following treatment with a PD-1/PD-L1 immune checkpoint inhibitor. This study will assess the efficacy and tolerability of a fixed dose of 800 mg of CX-072 every three weeks in combination with ipilimumab at the full labelled combination dose and schedule of 3 mg/kg every three weeks for four cycles. CX-072 therapy will be continued once every two weeks after the completion of the combination phase until disease progression. The primary objective is overall response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with secondary objectives evaluating the safety and tolerability of CX-072. The cohort utilizes a Simon 2 Stage design with approximately 40 patients being enrolled into Stage 1 with additional patients being enrolled into Stage 2, pending the outcome of Stage 1. CytomX anticipates initial data from Stage 1 in 2020.

Additional information on this trial is available at ClinicalTrials.gov using the identifier NCT03993379.

Unmet Need in Relapsed Refractory Melanoma

Melanoma is a life-threatening form of skin cancer. The incidence of melanoma has been increasing over the last 40 years, with about 150K newly diagnosed patients across major markets in 2018. In the unresectable/metastatic setting, approximately 60% of melanoma patients will receive immune checkpoint blockade (~35% of BRAF+ patients and ~75% of BRAF WT) yet ~85% of those patients will progress. For patients with unresectable/metastatic melanoma who progress after PD-1/L1 therapy, there are limited treatment options available.

Updated Top-Line Results from the Phase 1 PROCLAIM-CX-072-001 Ipilimumab Combination Study

This open-label, dose-finding study evaluated CX-072 in combination with ipilimumab in patients with advanced solid tumors. Preliminary data from this trial was first presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting and enrollment is complete. Updated data, as of an October 2019 snapshot, showed that among 27 evaluable patients who received ipilimumab (3, 6 or 10 mg/kg) combined with CX-072 (0.3, 1, 3 or 10 mg/kg), the disease control rate (stable disease or better) was 37%. Five patients achieved confirmed objective responses by RECIST v1.1 including one complete response, for an ORR of 19% in these heavily pretreated patients. The median duration of response was 14.6 months (1.9 – 21.2 months) with 4 of the 5 responders still on treatment as of the latest data snapshot.

The recommended combination dose for further investigation is 3 mg/kg of ipilimumab and 10 mg/kg of CX-072 (dose equivalent of 800 mg). This combination was generally well tolerated with no new safety signals observed. Of the 27 patients treated across all doses, Grade 3/4 treatment related adverse events (TRAE) were reported in 9 (33%) patients and Grade 3/4 immune related adverse events (irAEs) were reported in 6 (22%) patients. Of the 20 patients treated with ipilimumab at 3 mg/kg at varying doses of CX-072, Grade 3/4 TRAEs were reported in 5 (25%) patients and Grade 3/4 irAEs were reported in 3 (15%) patients.

The Company is preparing data from the Phase 1 PROCLAIM-CX-072-001 study for publication.

Curis to Release Third Quarter Financial Results and Hold Conference Call on November 5, 2019

On October 29, 2019 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the Company will release its third quarter financial results on Tuesday, November 5, 2019, after the close of US markets (Press release, Curis, OCT 29, 2019, View Source [SID1234549965]). Management will host a conference call on the same day at 4:30 p.m. ET.

To access the live conference call, please dial (888) 346-6389 from the United States or (412) 317-5252 from other locations, shortly before 4:30 p.m. ET. The conference call can also be accessed on the Curis website at www.curis.com in the ‘Investors’ section. A replay of the financial results conference call will be available on the Curis website shortly after completion of the call.