On March 1, 2019 Medtronic plc (NYSE:MDT), the global leader in medical technology, reported it will participate in the 39th Annual Cowen and Company Healthcare Conference on Monday, March 11, 2019, in Boston, Massachusetts (Press release, Medtronic, MAR 1, 2019, View Source;p=RssLanding&cat=news&id=2389717 [SID1234533863]).

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Bob White, executive vice president and president of Medtronic’s Minimally Invasive Therapies Group (MITG), will answer questions about the company beginning at 11:20 a.m. EDT (10:20 a.m. CDT).

A live audio webcast of the presentation will be available on March 11, 2019, by clicking on the Investor Events link at View Source An archive of the session will be available on the same webpage later in the day.

On March 1, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported early results from the ongoing dose-escalation stage of the first-in-human REVEAL Phase 1/2 clinical study evaluating the safety and efficacy of NKTR-262, a novel toll-like receptor (TLR) 7/8 agonist, in combination with bempegaldesleukin* (NKTR-214 or bempeg), a CD122-preferential IL-2 pathway agonist (Press release, Nektar Therapeutics, MAR 1, 2019, View Source [SID1234533879]). The results were presented today in an oral session at the 2019 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium by Dr. Adi Diab, Assistant Professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center (Oral Abstract Session B, Abstract #28, 1:00 p.m. – 2:15 p.m. PT).

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NKTR-262 is designed to induce the body’s innate immune response to prime antigen-specific cytotoxic T cells to fight cancer. Bempegaldesleukin is designed to activate the adaptive immune system to expand and proliferate these specific cancer-fighting T cells in the tumor microenvironment.

"We’re excited by the preliminary data from the REVEAL study which demonstrate desirable changes in the tumor micro-environment consistent with the activation of both the innate and adaptive immune responses induced by NKTR-262 and bempeg," said Dr. Jonathan Zalevsky, Chief Scientific Officer at Nektar. "The early data from REVEAL demonstrate that a comprehensive approach to activating the body’s immune system can drive abscopal anti-tumor responses even in the absence of a checkpoint inhibitor. We are looking forward to the ongoing dose-escalation and planned expansion of the study."

The dose-escalation phase of REVEAL is ongoing. As of January 23, 2019, 13 patients were enrolled that were refractory to all prior therapies known to confer clinical benefit. Key highlights of the data presentation are:

Maximum tolerated dose has not been reached and the dose escalation stage of the study is continuing.
Initial dose cohorts of NKTR-262 intra-tumoral injection combined with fixed dose of bempeg IV Q3W were well tolerated. Treatment-related adverse events were transient, characterized by Grade 1-2 flu-like symptoms (69.2%), rash (46.2%), fatigue (46.2%), pruritus (46.2%) and nausea (30.8%). There were no immune-mediated adverse events or study discontinuations due to TRAEs.
Local gene expression analysis of the injected tumor along with analysis of blood cells in system circulation demonstrated comprehensive activation of the immune system, including increases in the Type I interferon pathway and induction of CD4+, CD8+ and NK cell proliferation.
Early evidence of clinical benefit including abscopal responses in non-injected lesions was observed in the dose-escalation cohort. 11 of 13 patients in dose-escalation were evaluable for efficacy with at least one on treatment scan. 2 out of 5 evaluable patients with relapsed/refractory (R/R) melanoma who progressed on more than one prior checkpoint or I-O therapy experienced confirmed partial responses with 100% and 50% reductions in target lesions per RECIST 1.1, respectively. 2 out of 2 heavily pre-treated Stage IV leiomyosarcoma patients and 1 heavily pre-treated triple negative breast cancer patient experienced stable disease as best response.
A copy of the full data presentation made by Dr. Diab is available on Nektar’s corporate website at View Source

Analyst Call
Nektar will host an analyst conference call featuring Dr. Adi Diab and company management on Friday, March 1, 2019 at 3:00 p.m. PT during the 2019 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium. The conference call may be accessed by dialing 877-881-2183 (toll-free) or 970-315-0453 (international) with the conference call passcode 6970019. The webcast and slides for the conference call can be accessed through a link posted on the Investors section of the Nektar website at View Source The webcast of the conference call will be available for replay through April 1, 2019.

About Nektar Phase 1/2 REVEAL Study
REVEAL is a Nektar-sponsored, open-label, multicenter, dose escalation and dose expansion study evaluating the combination of NKTR-262 administered as an initial intratumoral injection followed by bempeg administered as an IV infusion systemically (doublet). In the Phase 2 expansion, the study also may evaluate the doublet combination with nivolumab (triplet). During the dose escalation phases, recommended Phase 2 dose (RP2D) regimens of the doublet and/or triplet combinations will be established. Following dose escalation, the dose expansion phase will evaluate the doublet and/or triplet combinations in up to 350 patients who have been diagnosed with a range of locally advanced or metastatic cancers including: melanoma, Merkel cell carcinoma, triple-negative breast cancer, ovarian cancer, renal cell carcinoma, colorectal cancer, urothelial carcinoma, or sarcoma. For more information, please visit View Source and search NCT03435640.

About Bempegaldesleukin (NKTR-214)
Bempegaldesleukin is an investigational, first-in-class, CD122-preferential IL-2 pathway agonist designed to provide rapid activation and proliferation of cancer-killing immune cells, known as CD8+ effector T cells and natural killer (NK) cells, without over activating the immune system. Bempegaldesleukin stimulates these cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3 Bempegaldesleukin has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

About NKTR-262
Cancer treatments that couple pharmacological activation of tumor antigen presentation with activation and expansion of CD8+ T and natural killer (NK) cells in the tumor environment have the potential to induce an effective anti-tumor immune response in patients. NKTR-262 is a novel small molecule agonist designed to activate toll-like receptors (TLRs). Intratumoral delivery of NKTR-262 promotes TLR activation to induce the development of antigen-specific immunity by initiating the process by which the immune system generates antigen-specific cytotoxic T cells to the patient’s specific tumor.4 Bempeg targets CD122 specific receptors found on the surface of these cancer-killing immune cells, known as CD8+ effector T cells. By first generating antigen-specific cytotoxic T cells with NKTR-262 and then growing these CD8+ effector T cells with bempeg, the patient’s entire immunity cycle can potentially be engaged to fight cancer. In preclinical studies, a single intratumoral dose of NKTR-262, administered in combination with bempeg, resulted in complete abscopal tumor regressions in multiple mouse syngeneic tumor models.5

On March 1, 2019 Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that its Board of Directors declared a quarterly cash dividend of $0.53 per share, payable on April 22, 2019 to shareholders of record of Quest Diagnostics common stock on April 8, 2019 (Press release, Quest Diagnostics, MAR 1, 2019, View Source [SID1234533880]).

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On March 1, 2019 ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that its Phase 3 FORWARD I trial evaluating the safety and efficacy of mirvetuximab soravtansine compared to chemotherapy in patients with folate receptor alpha (FRα)-positive, platinum-resistant ovarian cancer did not meet its primary endpoint of progression-free survival (PFS) in either the entire study population or in the pre-specified subset of patients with high FRα expression (Press release, ImmunoGen, MAR 1, 2019, View Source [SID1234533865]).

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"Even though FORWARD I did not meet its primary endpoint, I continue to be impressed with the efficacy and tolerability of mirvetuximab soravtansine in ovarian cancer patients, especially in the subset with high FRα expression," said Dr. Kathleen Moore, Associate Director of Clinical Research at the Stephenson Cancer Center at the University of Oklahoma. "I look forward to continuing to work with ImmunoGen to analyze the Phase 3 data and determine the most appropriate path to bringing mirvetuximab soravtansine to those patients who benefit most from it."

The FORWARD I Phase 3 trial randomized 366 patients 2:1 to receive either mirvetuximab soravtansine or the physician’s choice of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel). Eligibility criteria included patients with platinum-resistant ovarian cancer that expressed medium or high levels of FRα who have been treated with up to three prior regimens. The primary endpoint of this study was PFS, which was assessed using the Hochberg procedure in the entire study population and in the subset of patients with high FRα expression. The Hochberg procedure enables the simultaneous testing of two overlapping populations. Under this statistical analysis plan, if the p-value of the primary endpoint in either population is greater than 0.05, the p-value in the other population needs to be less than or equal to 0.025 to achieve statistical significance.

"Based upon the efficacy signals we observed in the high FRα subset with PFS, confirmed overall response rate and overall survival, we are conducting additional analyses to further evaluate the potential benefit of mirvetuximab soravtansine for FRα-positive platinum-resistant ovarian cancer," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "We want to thank the patients who participated in this trial, the clinical investigators, and the support staff for their hard work, as we continue to pursue our goal of finding innovative cancer treatments for patients in need."

Key findings from FORWARD I are as follows:

In the entire study population, the confirmed overall response rate was higher for mirvetuximab soravtansine than for chemotherapy (22% vs 12%, p-value 0.015), without a significant difference in the primary endpoint of PFS (HR 0.98, p-value 0.897) or overall survival (HR 0.81, p-value 0.248).
In the pre-specified high FRα subgroup (218/366, 60%)
PFS was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.69, p-value 0.049). Given that the p-value in the entire study population exceeded 0.05, the statistical analysis plan for the study required the p-value in the high subset to be less than or equal to 0.025 to achieve statistical significance.
Confirmed overall response rate was higher for mirvetuximab soravtansine than for chemotherapy (24% vs 10%, p-value 0.014).
Overall survival was longer in patients who received mirvetuximab soravtansine compared with chemotherapy (HR 0.62, p-value 0.033).
Mirvetuximab soravtansine was well-tolerated, with fewer patients experiencing grade 3 or greater adverse events (46% vs 61%), fewer dose reductions (20% vs 31%), and fewer discontinuations due to drug-related adverse events (5% vs 8%) compared with chemotherapy.
The safety profile of mirvetuximab soravtansine was confirmed, with the most common adverse events including nausea (54% all grades; 2% grade 3 or greater), diarrhea (44% all grades; 4% grade 3 or greater), and blurred vision (43% all grades; 3% grade 3 or greater).
"This study with mirvetuximab did not result in the outcome that we had hoped for in platinum-resistant patients. We will further assess the data from FORWARD I to determine potential next steps with a monotherapy approach. In parallel, we have generated encouraging data with mirvetuximab combination regimens and will evaluate our ongoing studies as an independent path forward to support a registration in ovarian cancer," said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. "ImmunoGen is in a strong financial position with approximately $295 million in cash on our balance sheet, and we will continue to advance our portfolio of next-generation ADCs, which includes three additional development candidates targeting a range of tumor types in both hematologic malignancies and solid tumors."

ImmunoGen intends to present additional results from FORWARD I at an upcoming medical meeting.

CONFERENCE CALL INFORMATION
ImmunoGen will host a conference call on March 1, 2019 at 8 a.m. ET to discuss the top-line findings from the FORWARD I trial. To access the live call by phone, dial 334-323-0522; the conference ID is 7188781. The call may also be accessed through the "Investors and Media" section of the Company’s website, www.immunogen.com. Following the live webcast, a replay of the call will be available at the same location through March 15.

ABOUT FORWARD I
FORWARD I is a Phase 3 trial in which 366 patients were randomized 2:1 to receive either mirvetuximab soravtansine or the physician’s choice of single-agent chemotherapy (pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel). Eligible patients were diagnosed with platinum-resistant ovarian cancer that expresses medium or high levels of FRα and were treated with up to three prior regimens. The primary endpoint of this study was progression free survival (PFS), which was assessed in the entire study population and in the subset of patients with high FRα expression. ImmunoGen estimates that 12,000-14,000 patients per year in the U.S. meet these criteria, with a comparable number in the major markets in Europe.

ImmunoGen partnered with the GOG Foundation Inc., a leader in clinical research in gynecologic malignancies, on FORWARD I, which was conducted in North America and Europe. This trial was intended to support full marketing approval of mirvetuximab soravtansine for patients with platinum-resistant ovarian cancer.

ABOUT MIRVETUXIMAB SORAVTANSINE
Mirvetuximab soravtansine (IMGN853) is the first folate receptor alpha (FRα)-targeting ADC. It uses a humanized FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, DM4, to kill the targeted cancer cells.

On March 1, 2019 Compugen Ltd. (NASDAQ: CGEN), a clinical-stage cancer immunotherapy company and leader in predictive target discovery, reported that its Phase 1 clinical trial evaluating COM701, a first-in-class therapeutic antibody targeting PVRIG, was featured in a trial-in-progress at The ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium (Press release, Compugen, MAR 1, 2019, View Source [SID1234533881]). In poster titled "A Phase 1 Study Evaluating COM701 in Patients With Advanced Solid Tumors," the Company reported that the third single subject dose cohort has been completed with no dose-limiting toxicities (DLTs) reported. Clinical and laboratory assessment for safety and tolerability is ongoing for the fourth dosing cohort. The poster presented at the symposium is available on Compugen’s website.

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"We continue to see significant interest in the study from investigators as they recognize the potential and differentiation of COM701 relative to other checkpoint inhibitors in development," said Henry Adewoye, M.D., Chief Medical Officer at Compugen. "After recently adding Massachusetts General Hospital and the University of Chicago, two additional leading medical centers with significant experience in immuno-oncology, we now have five sites recruiting patients for this Phase 1 study. Patient enrollment is also on track and we expect to complete enrollment of both the monotherapy and dual combination dose escalation arms of the study this year."

The sites currently recruiting patients are: The START center in San Antonio, Texas; The University of Tennessee West Cancer Center in Memphis, Tennessee; Sarah Cannon Research Institute in Nashville, Tennessee; Massachusetts General Hospital in Boston, Massachusetts; and the University of Chicago in Chicago, Illinois. The study is expected to include up to ten sites and enroll approximately 140 patients.

Updated information on the COM701 Phase 1 clinical study will be next featured in a trial-in-progress poster at The AACR (Free AACR Whitepaper) Annual Meeting 2019 taking place March 29-April 3, 2019 at the Georgia World Congress Center, Atlanta, GA.

About the COM701 Phase 1 Study

This Phase 1 open-label clinical trial is designed to assess the safety and tolerability of administering escalating doses of COM701 monotherapy as well as combination administration with a PD-1 inhibitor in patients with advanced solid tumors. Additionally, the trial will evaluate evidence of preliminary antitumor activity of COM701 as a monotherapy as well as in combination with a PD-1 inhibitor in patients with selected tumor types, including non-small cell lung cancer, ovarian cancer, breast cancer and endometrial cancer. Additional information is available here.