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Updated antitumor activity and safety of FPA144, an ADCC-enhanced, FGFR2b isoform-specific monoclonal antibody, in patients with FGFR2b+ gastric cancer

Background: FGFR2b-overexpressing gastric cancer is characterized by poor prognosis. FPA144, a humanized monoclonal IgG1 antibody that specifically binds to and blocks FGFR2b, has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). FPA144-001 is a two-part Phase 1 study of FPA144 monotherapy in patients with advanced solid tumors, including gastric and gastroesophageal cancers (GEJ cancers).
Methods: Part 1A was a 3+3 design to assess safety and PK and to establish a recommended dose (RD) of FPA144. Patients with gastric cancer were enrolled in Part 1B to assess PK in gastric cancer. Part 2 includes 4 cohorts of gastric cancer patients with either high, moderate, low or no FGFR2b overexpression based on a centralized immunohistochemistry (IHC) assay. Here, we describe results of gastric cancer patients that highly overexpress FGFR2b (FGFR2b+ High) enrolled in Parts 1 and 2 of the study.
Results: As of October 28, 2016, 18 FGFR2b+ High (IHC 3+ ³10% tumor membrane staining) patients were enrolled in the study. 12 of these patients received the RD of 15 mg/kg every 2 weeks. Enrolled patients received a median of 3 prior treatment regimens. Fatigue (22.2%, none ³ gr 3) and infusion reaction (16.7%, 5.6% gr 3) were the most common treatment-related AEs. Treatment-related SAEs were reported in 2 patients: Grade 2 ulcerative keratitis and Grade 3 infusion reaction. There were 5 PRs, 4 confirmed and 1 unconfirmed. Disease control (PR+SD) was 55.6%, including a confirmed ORR of 22% with median DOR of 15.4 weeks. ctDNA analysis of a responding patient revealed baseline elevated FGFR2 gene copy (165 copies in the blood, mutation allele burden 66%) that decreased after monotherapy (nadir 75 copies, mutation allele burden 38.5%) corresponding with clinical response, serum tumor markers and near complete response on PET imaging.
Conclusions:
The demonstration of activity and an acceptable safety profile supports further development of FPA144 in patients with FGFR2b+ tumors. FGFR2 gene amplification detected in ctDNA may provide a non-invasive diagnostic test for patient selection. Updated data will be presented. NCT02318329.

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EISAI TO PRESENT ABSTRACTS ON ONCOLOGY PRODUCTS AND PIPELINE AT 53RD ASCO ANNUAL MEETING RESULTS OF STUDY OF LENVIMA(R) (LENVATINIB) IN HEPATOCELLULAR CARCINOMA TO BE PRESENTED IN ORAL SESSION

On May 18, 2017 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that a series of abstracts highlighting new study results for its in-house discovered lenvatinib mesylate (selective inhibitor of receptor tyrosine kinases (RTKs) with a novel binding mode, product name: Lenvima / Kisplyx, "lenvatinib") and eribulin mesylate (halichondrin class microtubule dynamics inhibitor, product name: Halaven, "eribulin"), as well as H3B-8800, a splicing modulator discovered by Eisai’s U.S. research subsidiary H3 Biomedicine Inc., will be presented during the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), taking place in Chicago, the United States, from June 2 to 6, 2017 (Press release, Eisai, MAY 18, 2017, View Source [SID1234519265]).

Detailed data regarding the results of a Phase III clinical trial (Study 304) of lenvatinib compared with sorafenib as a first-line treatment for patients with unresectable hepatocellular carcinoma, which has already achieved its primary endpoint, will be presented orally at the ASCO (Free ASCO Whitepaper) Annual Meeting. This presentation is scheduled to take place on Sunday, June 4, 8:12 AM local time, in Hall D2.

Major poster presentations will include a highlight of the results of a Phase Ib/II clinical trial (Study 111) of lenvatinib in combination with the anti-PD-1 antibody pembrolizumab for the treatment of patients with endometrial carcinoma, and the results of a Phase I clinical trial of H3B-8800 in patients with advanced myeloid malignancies.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. The company will continue to create innovation in the development of new drugs based on cutting-edge cancer research, as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

Oral Presentations:
Product Abstract title and scheduled presentation date and time (local time)
Lenvatinib

Abstract No: 4001 Phase 3 trial of lenvatinib (LEN) vs sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC)
Oral Presentation | June 4 (Sun), 8:12-8:24 AM
Major Poster Presentations:
Product Abstract title and scheduled presentation date and time (local time)
Lenvatinib

Abstract No: 5598 A Phase Ib/II Trial of Lenvatinib (LEN) Plus Pembrolizumab (Pembro) in Patients (Pts) With Endometrial Carcinoma
Poster Presentation | June 3 (Sat), 1:15-4:45 PM
Lenvatinib

Abstract No: TPS4595 A Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination with Everolimus or Pembrolizumab vs Sunitinib Alone in First-Line Treatment of Patients with Advanced Renal Cell Carcinoma
Poster Presentation | June 4 (Sun), 8:00-11:30 AM
Lenvatinib

Abstract No: 10544 Single-agent Dose-finding Cohort of a Phase 1/2 Study of Lenvatinib (LEN) in Children and Adolescents with Refractory or Relapsed Solid Tumors
Poster Presentation | June 4 (Sun), 8:00-11:30 AM
Eribulin

Abstract No: 6603 Validity and Reliability of Four Value Frameworks for Cancer Drugs

Poster Presentation | June 5 (Mon), 1:15-4:45 PM
H3B-8800

Abstract No: TPS7075 H3B-8800-G0001-101: A first in human phase I study of a splicing modulator in patients with advanced myeloid malignancies
Poster Presentation | June 5 (Mon), 8:00-11:30 AM

GlycoMimetics Announces High Overall Response Rates, Low Induction Mortality, Promising Initial Survival Outcomes, and Supportive Biomarker Data from Phase 1/2 Trial of GMI-1271 in AML

On May 18, 2017 GlycoMimetics, Inc. (NASDAQ: GLYC) reported the release of abstracts containing new data from the ongoing Phase 2 clinical trial of its product candidate GMI-1271, an E-selectin antagonist, in patients with acute myeloid leukemia (AML) (Press release, GlycoMimetics, MAY 18, 2017, View Source [SID1234519253]). The data will be presented at the June annual meetings of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Hematology Association (EHA) (Free EHA Whitepaper). The data released by ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper), which reflect a late-January analysis, will be updated in posters presented at both meetings.

In the ongoing Phase 2 trial, AML patients treated with GMI-1271, combined with chemotherapy, continue to experience higher-than-expected remission rates and lower-than-expected induction-related mortality rates in both arms of the trial. In addition, researchers have observed that baseline expression of the E-selectin ligand biomarker on leukemia cells was predictive of clinical response and tied to greater likelihood of achieving remission in the cohort of AML patients with relapsed/refractory disease, which supports the mechanism of action of GMI-1271. Treatment with GMI-1271 continues to be well tolerated, with no obvious incremental toxicity observed when GMI-1271 is added to chemotherapy.

According to Helen Thackray, MD, Chief Medical Officer, "The data has consistently shown good tolerability and high remission rates as well as lower than expected 30- and 60-day mortality rates in early evaluations of patients. We are increasingly confident that our investigational drug, GMI-1271, may play a role in addressing unmet needs in this cancer. It is particularly noteworthy to see in the relapsed/refractory cohort that patients who have higher levels of the E-selectin ligand biomarker on their leukemic blasts appear to be more likely to achieve remission of their disease. This observation builds directly on what we and others have reported in the preclinical and clinical settings about the key role E-selectin plays in many forms of cancer, including AML. Importantly, this provides what we believe is the first direct clinical evidence of the potential benefit of targeting of E-selectin in this difficult-to-treat population of AML patients."

Relapsed or Refractory Disease Arm: Abstract Data

Consistent with GlycoMimetics’ prior published research, the addition of GMI-1271 to mitoxantrone, etoposide and cytarabine (MEC) chemotherapy has been well-tolerated, with patients achieving a high overall response rate (ORR), low induction mortality, and promising initial survival outcomes. The data show that baseline expression of the E-selectin ligand biomarker was predictive of response. GlycoMimetics believes these results are better than what would be expected in this population, based on published historical controls in similar patients.

Highlights of the data reported in the published abstract include:

47 patients were enrolled.
30- and 60-day mortality were 0 and 7%, respectively.
ORR was 21/42 evaluable (50%).
Median Overall Survival in the Phase 1 portion was 7.6 months.
The median E-selectin ligand binding at baseline was 35% of blasts (range, 1-75%) and, importantly, was higher in those achieving remission.
The data from the ongoing Phase 2 trial were submitted to the U.S. Food and Drug Administration (FDA). As announced yesterday, GMI-1271 was granted Breakthrough Therapy designation from the FDA for the treatment of adult AML patients with relapsed/refractory disease. The FDA had previously granted Orphan Drug designation and Fast Track Status for GMI-1271 for the treatment of AML.

Newly Diagnosed, Treatment-Naïve, Elderly Arm: Abstract Data

In the published abstract, data reflects 17 of 24 enrolled and evaluable elderly patients. Highlights from the abstract include:

The remission rate (CR/CRi) was 12/17 (71%).
CR/CRi rate was 75% for patients with de novo disease and 67% for patients with secondary AML.
GlycoMimetics noted that the safety profile of the investigational drug, GMI-1271, in combination with chemotherapy is encouraging. Outcomes for elderly patients with AML remain poor, and tolerability of treatments is a key concern.

Deciphera Pharmaceuticals to Report Phase 1 Clinical Study Results with DCC-2618 at the 2017 American Society of Clinical Oncology Annual Meeting

On May 18, 2017 Deciphera Pharmaceuticals, a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that a poster presentation that includes updated results from the ongoing Phase 1 clinical study of DCC-2618, the company’s pan-KIT and PDGFR inhibitor, will be presented at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 2 – 6, 2017, in Chicago, IL (Press release, Deciphera Pharmaceuticals, MAY 18, 2017, View Source [SID1234519252]). Details of the presentation are as follows:

Poster Title: Pharmacokinetic-driven phase 1 study of DCC-2618 a pan-KIT and PDGFR inhibitor in patients with gastrointestinal stromal tumor (GIST) and other solid tumors.
Author: Filip Janku, M.D., Ph.D., The University of Texas MD Anderson Cancer Center
Session: Poster Discussion Session: Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics
Abstract #: 2515
Date and Time: Monday, June 5, 2017, 8:00 AM – 11:30AM (CST)
Poster Discussion Session: Monday, June 5, 2017 11:30 AM-12:45 PM (CST)

"We are very pleased to present these important results and to provide an update on the clinical development of DCC-2618, our pan-KIT and PDGFR inhibitor in development for difficult to treat, KIT and/or PDGFRα-driven cancers with limited therapeutic options," said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer.

"These maturing data confirm earlier results presented at the 2016 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics," added Oliver Rosen, M.D., Deciphera’s Chief Medical Officer. "The encouraging clinical activity achieved in patients with a broad spectrum of mutations and prior therapies in our Phase 1 study supports the impressive translational data presented last month at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting".

About DCC-2618
DCC-2618 is currently in a first-in-human Phase 1 clinical trial. DCC-2618 is a pan-KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, glioblastoma multiforme and systemic mastocytosis.

SYROS TO PRESENT ON SY-1425 IN COMBINATION WITH STANDARD-OF-CARE AND TARGETED THERAPIES IN GENOMICALLY DEFINED SUBSETS OF AML AND MDS PATIENTS

On May 18, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that the Company will present preclinical data on SY-1425, its oral first-in-class selective retinoic acid receptor alpha (RARα) agonist, in combination with hypomethylating agents and anti-CD38 therapies in genomically defined subsets of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place June 22-25 in Madrid, Spain (Press release, Syros Pharmaceuticals, MAY 18, 2017, View Source;p=irol-newsArticle&ID=2273936 [SID1234519251]).

Details on the presentation are as follows:

Date & Time: Friday, June 23, from 5:15 – 6:45 p.m. CEST
Presentation Title: Mechanistically Informed Combinations of SY-1425, a Potent and Selective RARα Agonist, with Hypomethylating or Anti-CD38 Targeted Agents in AML and MDS
Session Title: Acute myeloid leukemia – Biology 2
Presenter: Michael R. McKeown, Ph.D., Senior Scientist, Translational Medicine, Syros
Abstract Number: P188
Location: IFEMA – Feria de Madrid, Poster area (Hall 7)

SY-1425 is currently in a Phase 2 clinical trial exploring its safety and efficacy as both a monotherapy and in combination with azacitidine, a standard-of-care hypomethylating agent, in subsets of AML and MDS patients with high expression of RARA pathway-associated genes RARA and IRF8.