On October 19, 2018 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that intracranial efficacy data from the Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial showed improved intracranial progression-free survival (PFS) and intracranial objective response rate (ORR) with ALUNBRIG (brigatinib) compared to crizotinib among anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) patients (Press release, Takeda, OCT 19, 2018, View Source [SID1234529988]). Data for these secondary endpoints will be presented in a poster discussion at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress on Friday, October 19 at 2:00 p.m. CET in Munich, Germany. These results further support ALUNBRIG as a potential treatment for adults with ALK+ locally advanced or metastatic NSCLC who had not received a prior ALK inhibitor. ALUNBRIG is currently not approved as first-line therapy for advanced ALK+ NSCLC.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"ALK+ NSCLC often spreads to the brain, so having options that can clearly demonstrate efficacy both in the brain and systemically is important for physicians and their patients," said Sanjay Popat, PhD, FRCP, Medical Oncologist, Royal Marsden Hospital. "The ALTA-1L trial showed that treatment with brigatinib significantly delayed progression of disease in the brain compared to crizotinib, and we look forward to sharing the clinical evidence with the medical community at ESMO (Free ESMO Whitepaper)."

In the first interim analysis of the ALTA-1L trial, intracranial PFS was significantly improved with ALUNBRIG compared to crizotinib in the Intention to Treat population (ITT) (Hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.24−0.70; log-rank P=0.0006) and the population with baseline brain metastases (HR: 0.27, 95% CI: 0.13−0.54; log-rank P<0.0001). Among patients with brain metastases at baseline, ALUNBRIG reduced the risk of progression in the brain or death by 73 percent. Intracranial PFS in patients without brain metastases at baseline is not yet mature as of this first interim analysis.

Treatment with ALUNBRIG also demonstrated an improved intracranial ORR compared to crizotinib. For patients with measurable brain metastases at baseline, 78 percent achieved confirmed intracranial OR in the ALUNBRIG arm versus 29 percent in the crizotinib arm. For patients with non-measurable brain metastases at baseline, 67 percent achieved confirmed intracranial OR in the ALUNBRIG arm versus 17 percent in the crizotinib arm.

In addition, ALUNBRIG significantly delayed both central nervous system (CNS) progression (without prior systemic progression) and systemic progression (without prior CNS progression) compared to crizotinib. Baseline factors related to the CNS, such as the proportion of patients with baseline brain metastases, mean number of brain metastases, and prior brain radiotherapy, including type, were balanced among patients in the two study arms. The safety profile associated with ALUNBRIG in the ALTA-1L trial was generally consistent with the existing U.S. prescribing information.

"CNS disease presents a significant burden for patients with ALK+ NSCLC," said David Kerstein, MD, Global Clinical Lead for Brigatinib and Lung Cancer Clinical Portfolio Strategy Lead, Takeda. "These additional intracranial efficacy results from the ALTA-1L trial build upon activity previously reported with ALUNBRIG in patients with brain metastases in the post-crizotinib setting and demonstrate Takeda’s dedication to research that aims to improve outcomes for those living with this serious disease."

These data build on results recently presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC), which showed that treatment with ALUNBRIG resulted in superior PFS compared to crizotinib as assessed by a blinded independent review committee, corresponding to a 51 percent reduction in the risk of disease progression or death (HR: 0.49, 95% CI: 0.33−0.74]; log-rank P=0.0007).

Grade 3 to 5 treatment-emergent adverse events occurred in 61% of the patients in the brigatinib arm and 55% of the patients in the crizotinib arm. Most common grade 3 or greater treatment-emergent adverse events for brigatinib were increased blood creatine phosphokinase (16%), increased lipase (13%), hypertension (10%), and increased amylase (5%); and for crizotinib were increased alanine aminotransferase (9%), increased aspartate aminotransferase (6%), and increased lipase (5%).

About the ALTA-1L Trial
The Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial of ALUNBRIG in adults is a global, ongoing, randomized, open-label, comparative, multicenter trial, which enrolled 275 patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor. Patients received either ALUNBRIG, 180 mg once daily with seven-day lead-in at 90 mg once daily, or crizotinib, 250 mg twice daily. Blinded Independent Review Committee (BIRC)-assessed progression-free survival (PFS) was the primary endpoint. Secondary endpoints included objective response rate (ORR) per RECIST v1.1, intracranial ORR, intracranial PFS, overall survival (OS), safety and tolerability. A total of approximately 198 PFS events are planned at the final analysis of the primary endpoint in order to demonstrate a minimum of six months PFS improvement over crizotinib. The trial is designed with two pre-specified interim analyses for the primary endpoint – one at approximately 50 percent of planned PFS events and one at approximately 75 percent of planned PFS events.

About ALK+ NSCLC

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients. Approximately three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.

Takeda is committed to continuing research and development in NSCLC to improve the lives of the approximately 40,000 patients diagnosed with this serious and rare form of lung cancer worldwide each year.

About ALUNBRIG (brigatinib)

ALUNBRIG is a targeted cancer medicine discovered by ARIAD Pharmaceuticals, Inc., which was acquired by Takeda in February 2017. In April 2017, ALUNBRIG received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for ALK+ metastatic NSCLC patients who have progressed on or are intolerant to crizotinib. This indication is approved under Accelerated Approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. In July 2018, Health Canada approved ALUNBRIG for the treatment of adult patients with ALK+ metastatic NSCLC who have progressed on or who were intolerant to an ALK inhibitor (crizotinib). The FDA and Health Canada approvals of ALUNBRIG were primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial.

ALUNBRIG received Breakthrough Therapy Designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib and was granted Orphan Drug Designation by the FDA for the treatment of ALK+ NSCLC, ROS1+ and EGFR+ NSCLC.

The brigatinib clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with ALK+ NSCLC worldwide and the healthcare professionals who treat them. The comprehensive program includes the following clinical trials:

Phase 1/2 trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ALUNBRIG
Pivotal Phase 2 ALTA trial investigating the efficacy and safety of ALUNBRIG at two dosing regimens in patients with ALK+ locally advanced or metastatic NSCLC who had progressed on crizotinib
Phase 3 ALTA-1L, a global randomized trial assessing the efficacy and safety of ALUNBRIG in comparison to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor
Phase 2 single-arm, multicenter trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib
Phase 2 global, single-arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib
Phase 3 global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib
For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION (U.S.)

WARNINGS AND PRECAUTIONS

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with ALUNBRIG. In Trial ALTA (ALTA), ILD/pneumonitis occurred in 3.7% of patients in the 90 mg group (90 mg once daily) and 9.1% of patients in the 90→180 mg group (180 mg once daily with 7-day lead-in at 90 mg once daily). Adverse reactions consistent with possible ILD/pneumonitis occurred early (within 9 days of initiation of ALUNBRIG; median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7%. Monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly during the first week of initiating ALUNBRIG. Withhold ALUNBRIG in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). For Grade 1 or 2 ILD/pneumonitis, either resume ALUNBRIG with dose reduction after recovery to baseline or permanently discontinue ALUNBRIG. Permanently discontinue ALUNBRIG for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.

Hypertension: In ALTA, hypertension was reported in 11% of patients in the 90 mg group who received ALUNBRIG and 21% of patients in the 90→180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall. Control blood pressure prior to treatment with ALUNBRIG. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 hypertension despite optimal antihypertensive therapy. Upon resolution or improvement to Grade 1 severity, resume ALUNBRIG at a reduced dose. Consider permanent discontinuation of treatment with ALUNBRIG for Grade 4 hypertension or recurrence of Grade 3 hypertension. Use caution when administering ALUNBRIG in combination with antihypertensive agents that cause bradycardia.

Bradycardia: Bradycardia can occur with ALUNBRIG. In ALTA, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients in the 90 mg group and 7.6% of patients in the 90→180 mg group. Grade 2 bradycardia occurred in 1 (0.9%) patient in the 90 mg group. Monitor heart rate and blood pressure during treatment with ALUNBRIG. Monitor patients more frequently if concomitant use of drug known to cause bradycardia cannot be avoided. For symptomatic bradycardia, withhold ALUNBRIG and review concomitant medications for those known to cause bradycardia. If a concomitant medication known to cause bradycardia is identified and discontinued or dose adjusted, resume ALUNBRIG at the same dose following resolution of symptomatic bradycardia; otherwise, reduce the dose of ALUNBRIG following resolution of symptomatic bradycardia. Discontinue ALUNBRIG for life-threatening bradycardia if no contributing concomitant medication is identified.

Visual Disturbance: In ALTA, adverse reactions leading to visual disturbance including blurred vision, diplopia, and reduced visual acuity, were reported in 7.3% of patients treated with ALUNBRIG in the 90 mg group and 10% of patients in the 90→180 mg group. Grade 3 macular edema and cataract occurred in one patient each in the 90→180 mg group. Advise patients to report any visual symptoms. Withhold ALUNBRIG and obtain an ophthalmologic evaluation in patients with new or worsening visual symptoms of Grade 2 or greater severity. Upon recovery of Grade 2 or Grade 3 visual disturbances to Grade 1 severity or baseline, resume ALUNBRIG at a reduced dose. Permanently discontinue treatment with ALUNBRIG for Grade 4 visual disturbances.

Creatine Phosphokinase (CPK) Elevation: In ALTA, creatine phosphokinase (CPK) elevation occurred in 27% of patients receiving ALUNBRIG in the 90 mg group and 48% of patients in the 90 mg→180 mg group. The incidence of Grade 3-4 CPK elevation was 2.8% in the 90 mg group and 12% in the 90→180 mg group. Dose reduction for CPK elevation occurred in 1.8% of patients in the 90 mg group and 4.5% in the 90→180 mg group. Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor CPK levels during ALUNBRIG treatment. Withhold ALUNBRIG for Grade 3 or 4 CPK elevation. Upon resolution or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or at a reduced dose.

Pancreatic Enzyme Elevation: In ALTA, amylase elevation occurred in 27% of patients in the 90 mg group and 39% of patients in the 90→180 mg group. Lipase elevations occurred in 21% of patients in the 90 mg group and 45% of patients in the 90→180 mg group. Grade 3 or 4 amylase elevation occurred in 3.7% of patients in the 90 mg group and 2.7% of patients in the 90→180 mg group. Grade 3 or 4 lipase elevation occurred in 4.6% of patients in the 90 mg group and 5.5% of patients in the 90→180 mg group. Monitor lipase and amylase during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or at a reduced dose.

Hyperglycemia: In ALTA, 43% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 3.7% of patients. Two of 20 (10%) patients with diabetes or glucose intolerance at baseline required initiation of insulin while receiving ALUNBRIG. Assess fasting serum glucose prior to initiation of ALUNBRIG and monitor periodically thereafter. Initiate or optimize anti-hyperglycemic medications as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold ALUNBRIG until adequate hyperglycemic control is achieved and consider reducing the dose of ALUNBRIG or permanently discontinuing ALUNBRIG.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to pregnant women. There are no clinical data on the use of ALUNBRIG in pregnant women. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least 4 months following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of ALUNBRIG.

ADVERSE REACTIONS

Serious adverse reactions occurred in 38% of patients in the 90 mg group and 40% of patients in the 90→180 mg group. The most common serious adverse reactions were pneumonia (5.5% overall, 3.7% in the 90 mg group, and 7.3% in the 90→180 mg group) and ILD/pneumonitis (4.6% overall, 1.8% in the 90 mg group and 7.3% in the 90→180 mg group). Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis (1 patient each).

The most common adverse reactions (≥25%) in the 90 mg group were nausea (33%), fatigue (29%), headache (28%), and dyspnea (27%) and in the 90→180 mg group were nausea (40%), diarrhea (38%), fatigue (36%), cough (34%), and headache (27%).

DRUG INTERACTIONS

CYP3A Inhibitors: Avoid concomitant use of ALUNBRIG with strong CYP3A inhibitors. Avoid grapefruit or grapefruit juice as it may also increase plasma concentrations of brigatinib. If concomitant use of a strong CYP3A inhibitor is unavoidable, reduce the dose of ALUNBRIG.

CYP3A Inducers: Avoid concomitant use of ALUNBRIG with strong CYP3A inducers.

CYP3A Substrates: Coadministration of ALUNBRIG with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and loss of efficacy of CYP3A substrates.

USE IN SPECIFIC POPULATIONS

Pregnancy: ALUNBRIG can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus.

Lactation: There are no data regarding the secretion of brigatinib in human milk or its effects on the breastfed infant or milk production. Because of the potential adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with ALUNBRIG.

Females and Males of Reproductive Potential:

Contraception: Advise females of reproductive potential to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least 4 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 3 months after the final dose.

Infertility: ALUNBRIG may cause reduced fertility in males.

Pediatric Use: The safety and efficacy of ALUNBRIG in pediatric patients have not been established.

Geriatric Use: Clinical studies of ALUNBRIG did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients. Of the 222 patients in ALTA, 19.4% were 65-74 years and 4.1% were 75 years or older. No clinically relevant differences in safety or efficacy were observed between patients ≥65 and younger patients.

Hepatic or Renal Impairment: No dose adjustment is recommended for patients with mild hepatic impairment or mild or moderate renal impairment. The safety of ALUNBRIG in patients with moderate or severe hepatic impairment or severe renal impairment has not been studied.

Please see the full U.S. Prescribing Information for ALUNBRIG at www.ALUNBRIG.com

On October 19, 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 preliminary results from its ongoing Phase 1 clinical study of DCC-2618, the company’s broad-spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) as a proffered paper presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany (Press release, Deciphera Pharmaceuticals, OCT 19, 2018, View Source [SID1234529987]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are extremely pleased with the preliminary results presented today that we believe demonstrate the potential of DCC-2618 to provide improved, durable clinical benefit for GIST patients from second-line through fourth-line-plus," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "While the data set is still maturing, we believe the median progression free survival value of 42 weeks observed in second-line GIST patients strongly supports our planned randomized Phase 3 study, INTRIGUE, in second-line GIST patients, which we expect to initiate before the end of the year. In addition, the disease control rate and objective response rate observed with DCC-2618 in second-line GIST patients continues to exceed the values reported in previously published, centrally-read, registrational trials for sunitinib."

The presentation reported preliminary results with a cutoff date of August 31, 2018 that include investigator-assessed median progression free survival (mPFS), objective response rates by best response (ORR) and disease control rates at 3 months (DCR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 across 178 patients receiving DCC-2618 at doses of ≥100mg daily:

Notes: (1) Includes nine unconfirmed responses: 2nd line (n=1), 3rd line (n=3) and ≥4th line (n=5); (2) Does not reflect one PR reported after cutoff date, which would result in an ORR in 2nd line of 21% and an ORR in 2nd line and 3rd line combined of 22%; (3) Excludes five patients due to missing data at the time of data cutoff (n=2), lack of first tumor assessment (n=1), withdrawal of consent prior to first assessment (n=1) and unrelated death at C1D4 prior to first assessment (n=1); (4) 59 of 67 combined 2nd line and 3rd line patients received 150mg once daily; and (5) Censored patients for mPFS were 2nd line (58%), 3rd line (52%), 4th line and 4th line plus (35%) and 2nd and 3rd line (55%).

"The preliminary progression free survival data and objective response rates observed with DCC-2618 are very encouraging across all lines of therapy presented: second-, third-, and fourth-line and beyond," said Suzanne George, M.D., Director of Clinical Research, Center for Sarcoma and Bone Oncology and Senior Physician at the Dana Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School. "There is a clear unmet need for effective and well tolerated options for patients with metastatic GIST beyond the first-line."

Highlights from the proffered paper include:

Preliminary Clinical Activity in Second-, Third-, Fourth- and Fourth-Line-Plus GIST Patients Demonstrates the Potential for Durable Clinical Outcomes with DCC-2618

Progression Free Survival (mPFS): The mPFS values observed with DCC-2618 were 42 weeks in second-line patients and 40 weeks in third-line patients. Previously published results for approved therapies from centrally-read registrational trials reported a mPFS for sunitinib of 24 weeks in second-line patients and a mPFS for regorafenib of 21 weeks in third-line patients. In fourth- and fourth-line-plus patients, where there are currently no approved therapies, the observed mPFS with DCC-2618 was 24 weeks. Published studies have reported a mPFS of 4-6 weeks for similarly heavily pre-treated patients who did not receive an active therapy.
Disease Control Rate (DCR): The observed DCRs at three months of 79% in second-line patients and 83% in third-line patients exceed the previously published results for approved therapies from centrally-read registrational trials of 60% for sunitinib in second-line patients and 53% for regorafenib in third-line patients. The DCR observed for DCC-2618 in fourth-line and fourth-line-plus patients was 66%.
Objective Response Rate (ORR): The observed ORRs of 18% in second-line patients and 24% in third-line patients continue to exceed the previously published results for approved therapies from centrally-read registrational trials of 7% for sunitinib in second-line patients and 5% for regorafenib in third-line patients. These values do not include a partial response in one second-line patient that was observed after the cutoff date, which would result in an ORR in second-line patients of 21%. The ORR observed for DCC-2618 in fourth-line and fourth-line-plus patients was 9%.
Prolonged Treatment Duration in GIST Patients Receiving DCC-2618 – Cutoff Date of August 31, 2018

In the second-line cohort, as of the cutoff date, 17 patients received DCC-2618 at doses of ≥100mg daily for >6 months with 65% (11 of 17) of these patients remaining on study.
In the third-line cohort, as of the cutoff date, 20 patients received DCC-2618 at doses of ≥100mg daily for >6 months with 75% (15 of 20) of these patients remaining on study.
In the fourth-line and fourth-line-plus patients, as of the cutoff date, 46 patients received DCC-2618 at doses of ≥100mg daily for >6 months with 74% (34 of 46) of these patients remaining on study.
Updated Safety Data Continue to Demonstrate a Favorable Tolerability Profile for DCC-2618

For 178 GIST patients treated at doses above ≥100mg daily, DCC-2618 was generally well tolerated.
Among the treatment-emergent adverse events (TEAEs) reported by investigators (>10%), regardless of relationship to DCC-2618, the most common were: alopecia (50%), myalgia (44%), fatigue (43%), constipation (34%), hand-foot skin reaction (32%), nausea (30%), decreased appetite (28%), weight decreased (24%), abdominal pain (23%), diarrhea (23%) and lipase increase (23%).
Among the 178 GIST patients treated at doses above ≥100mg daily:
14% (24) patients experienced dose reductions due to TEAE.
11% (19) experienced treatment discontinuations due to TEAE.
A copy of the proffered paper will be available on the Deciphera Pharmaceuticals website in the Science section under "Presentations and Publications" located at www.deciphera.com. A copy of the updated Corporate Presentation will be available on the Deciphera Pharmaceuticals website in the Investor section under "Events and Presentations" located 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.

On October 19, 2018 Sensei Biotherapeutics, Inc., a clinical-stage biopharmaceutical company developing precision immuno-oncology therapies, announced today the results of the Phase 1 clinical trial evaluating the safety and immunogenicity of SNS-301 in patients with biochemically recurrent prostate cancer (BRPC) (Press release, Sensei Biotherapeutics, OCT 19, 2018, View Source [SID1234529986]). Patients in the clinical trial were antigen-positive for human aspartate β-hydroxylase (ASPH), a novel tumor-specific embryonic antigen, and selected using Sensei’s proprietary companion diagnostic. SNS-301, a first-in-class immunotherapy candidate targeting ASPH, is the lead clinical candidate in Sensei’s pipeline of innovative cancer immunotherapies created using Sensei’s SPIRIT platform. Results from the Phase 1 study of SNS-301 will be presented at a Poster Discussion session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, taking place October 19-23, 2018, in Munich, Germany.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The principal outcomes from this study further energize our strategy of pursuing next-generation targets, such as ASPH, combined with visionary bioengineering and precision medicine," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "Based on these positive results, we plan to initiate a Phase 2 trial for SNS-301 in various hematological malignancies and solid tumors in early 2019. We also plan to accelerate the development of our cell therapy programs targeting ASPH and other novel tumor-specific antigens."

"SNS-301’s strong anti-tumor immune activity was shown through increases in both ASPH-specific CD8+ T-cells and ASPH-specific B-cell responses," said Ildiko Csiki, M.D., Ph.D., Chief Medical Officer of Sensei Biotherapeutics. "Based on these compelling early data showing anti-tumor immune response, coupled with a favorable safety profile, we believe SNS-301 has the potential to benefit patients with ASPH-expressing tumors. In a Phase 2 setting, we plan to focus on head and neck cancer, myelodysplastic syndrome, and additional solid tumor indications."

In the multi-center Phase 1 clinical trial, SNS-301 was administered every 21 days via intradermal injection to BRPC patients using a fixed dose-escalation schema to establish the recommended Phase 2 dose. The clinical trial enrolled 12 patients who were confirmed to express ASPH using Sensei’s proprietary serum-based companion diagnostic test. Patients received between 8 to 23 doses of SNS-301 (with an average of 10 doses per patient) at the three different doses in the study, with the cohort of low-dose patients progressing through to the high dose, and the cohort of mid-dose patients escalating successfully to the high dose.

Data from the Phase 1 trial demonstrated a favorable safety profile, improvements in disease-related parameters, and ASPH-specific immune responses. Highlights of the safety and immunogenicity data presented at ESMO (Free ESMO Whitepaper) include:

At all three dose levels in the Phase 1 trial (2 x 1010, 1 x 1011, 3 x 1011 particles), SNS-301 was well tolerated with a favorable safety profile. No dose-limiting toxicities or grade 4-5 adverse events were observed in the trial.
Eight out of the 12 patients (75%) achieved improvements in PSA doubling time and/or absolute PSA level, leading to decreased PSA velocity and suggesting a disease stabilizing effect of SNS-301.
An average 8-to-10-fold increase in the percentage of ASPH-specific CD8+ T-cells was observed post-treatment, compared to baseline measurements. Peak antigen-specific T-cell levels were observed between 43 and 85 days from initial treatment. All seven patients that were evaluable for immune responses showed increases in ASPH-specific T-cells.
An average 5-to-7-fold increase in the percentage of ASPH-specific B-cell responses was observed post-treatment, compared to baseline measurements. Peak antigen-specific B-cell levels were observed between 64 and 106 days from initial treatment. All 12 patients enrolled had increases in ASPH-specific B-cells.
A strong corresponding increase in anti-ASPH antibody titers across patients correlated with B-cell response and a subsequent reduction in serum-based ASPH was observed.
The recommended Phase 2 dose was identified as the mid-dose (1 x 1011 particles) in the Phase 1 trial based on immunogenicity and PSA results of the three evaluated doses.
Sensei’s planned Phase 2 program will evaluate SNS-301 as monotherapy in hematological malignancies and as combination therapy with checkpoint inhibitors in multiple solid tumors, with clinical trials to be initiated in 2019.

About SNS-301
SNS-301 is a first-in-class cancer immunotherapy targeting human aspartate β-hydroxylase (ASPH), a cell surface enzyme that is normally expressed during embryonic development. Following embryonic development, the protein is no longer expressed in healthy adults. Expression of ASPH is uniquely upregulated in more than 20 different types of cancer and is related to cancer cell growth, cell motility and invasiveness. ASPH signaling occurs through the Notch pathway and expression levels in various tumors are inversely correlated with disease prognosis. SNS-301 is a bio-engineered, inactivated bacteriophage virus expressing a fusion protein of native bacteriophage GPD (Glyceraldehyde-3-phosphate dehydrogenase) protein and a selected domain of ASPH. SNS-301 is designed to overcome immune tolerance and induce robust and durable ASPH-specific humoral and cellular responses. SNS-301 is paired with a companion diagnostic to ensure appropriate patient selection and is delivered easily through an intradermal injection to aid in generating robust immune response.

On October 19, 2018 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 antagonists to improve immune cell trafficking to treat cancer and rare disease, reported results from a pilot study of X4P-001-IO in combination with Opdivo (nivolumab) in patients with clear cell renal cell carcinoma (ccRCC) who are non-responsive to the anti-PD-1 checkpoint inhibitor Opdivo alone (Press release, X4 Pharmaceuticals, OCT 19, 2018, View Source [SID1234529985]). The data will be presented at a Poster Discussion session at CThe data from this study demonstrate that the combination with X4P-001-IO and nivolumab has the potential to augment responses in patients who previously received the anti-PD-1 checkpoint inhibitor nivolumab alone," said Toni K. Choueiri, M.D. Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and lead investigator of the study. "This pilot study data requires validation in larger studies as we continue to seek treatments to address the larger population of cancer patients who do not adequately respond to checkpoint inhibitors."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Results were presented from the nine patients with advanced ccRCC enrolled in the pilot study (as of August 1, 2018) who were non-responsive to single agent Opdivo with either stable or progressive disease. Enrolled patients received X4P-001-IO (400 mg, oral, once daily) and continued to receive standard bi-weekly Opdivo therapy. Median duration of treatment with the combination was 3.7 months (range 1-15 months).

Highlights of the data presented at ESMO (Free ESMO Whitepaper) include:

X4P-001-IO in combination with Opdivo was tolerable in ccRCC patients. The most frequent drug related adverse events were diarrhea, nasal congestion, ALT/AST increase, dry eye, fatigue. No grade 4 or 5 adverse events occurred. All Grade 3/serious adverse events were manageable with appropriate intervention.
Combination therapy with X4P-001-IO and Opdivo exhibited anti-tumor activity in some patients with advanced ccRCC who were previously unresponsive to Opdivo monotherapy.
Four patients who had progressed on prior Opdivo monotherapy had a best response of stable disease with the additional X4P-001-IO to Opdivo treatment.
Of the five patients who were stable on prior Opdivo monotherapy, one had a partial response with combination therapy of X4P-001-IO and Opdivo.
Serum biomarker analyses identified significant early changes in cytokines and chemokines, including CXCL9, a chemoattractant ligand for cytotoxic T cell migration.
"These findings add to our clinical experience with X4P-001-IO and our growing understanding of combining CXCR4 antagonists with other agents, such as checkpoint inhibitors," said Ken Gorelick, M.D., Chief Medical Officer of X4 Pharmaceuticals. "X4 continues to explore the important role that CXCR4 antagonism may play in augmenting anti-tumor response in combination with other cancer therapeutic modalities, and therefore, potentially improve outcomes for cancer patients."

About X4P-001-IO in Cancer
X4P-001-IO is an investigational selective, oral, small molecule antagonist of C-X-C receptor type 4 (CXCR4). CXCR4 is a chemokine receptor present in abundance on certain immune cells and cancer cells and it plays a critical role in immune cell trafficking, infiltration and activation in the tumor microenvironment. CXCR4 signaling is disrupted in a broad range of cancers, facilitating tumor growth by allowing cancer cells to evade immune detection and creating a pro-tumor microenvironment. X4P-001-IO has the ability to help restore immunity within the tumor microenvironment and has the potential to enhance the anti-tumor activity of approved and emerging oncology agents, such as checkpoint inhibitors and targeted therapies. X4P-001-IO is being investigated in several clinical studies in solid tumors.

On October 19, 2018 Boehringer Ingelheim reported results from GioTag, a real-world retrospective study which examined the impact of first-line Giotrif/Gilotrif (afatinib) followed by osimertinib, in epidermal growth factor receptor mutation-positive (EGFR M+) non-small cell lung cancer (NSCLC) patients with acquired T790M mutations, the most common mechanism of resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) (Press release, Boehringer Ingelheim, OCT 19, 2018, View Source [SID1234529984]). The results showed that the sequential strategy was effective in delaying subsequent chemotherapy treatment and were published today in the journal Future Oncology.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

According to the study, the median time on treatment for sequential afatinib and osimertinib was 27.6 months. In this broad, real-world population, the clinical benefit was consistent across all patient subgroups, with particularly encouraging results seen in those with exon 19 deletion (Del19)-positive disease (median time on treatment 30.3 months) and Asian patients (median time on treatment 46.7 months). Additionally, the 2 year and 2.5 year overall survival (OS) rates were 78.9% and 68.8%, respectively.1

Among the patients included in this study, 15.3% had a poor performance status at the start of afatinib treatment (as defined by ECOG performance status ≥2), ordinarily precluding them from clinical trials.1

While osimertinib is an effective first-line treatment,2 there is a lack of approved subsequent TKI treatment options, and many patients progress to chemotherapy following osimertinib failure.1 The results suggest that the sequential strategy of afatinib and osimertinib might offer sustained clinical benefit to a substantial number of patients, prolonging the chemotherapy-free treatment period.1

"With more targeted treatment options becoming available, it is important to understand the impact of multiple lines of targeted therapies on patient outcomes," said Dr. Maximilian J. Hochmair, Medical Oncologist, Department of Respiratory and Critical Care Medicine, Otto Wagner Hospital and coordinating investigator in the trial. "The results of GioTag show that sequential treatment with afatinib and osimertinib is an attractive strategy in patients with EGFR mutation-positive NSCLC, offering a sustained clinical benefit to a substantial number of patients while – importantly – extending the time patients are kept off chemotherapy."

Dr. Victoria Zazulina, Global Head of Solid Tumour Oncology, Medicine at Boehringer Ingelheim, said, "We saw through a recent global survey published at WCLC that many physicians do not feel they have enough information to make informed treatment decisions on how to make the most of the available targeted treatments for patients with EGFR M+ NSCLC; in the absence of randomised data, real-world evidence may help inform treatment decisions. GioTag is the first global study in EGFR M+ NSCLC looking at the sequencing of targeted therapies as it is used in daily clinical practice. These results will provide more insights on the use of EGFR TKIs, looking beyond first-line to maximise overall longer-term impact of targeted therapies in NSCLC."

Results of a recent global survey of HCPs’ attitudes about sequencing treatments for EGFR M+ NSCLC patients are available here. Full results from the GioTag study will be presented at an upcoming medical conference later this year.