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SITC 2018: further analyses of the Phase II study of the combination of monalizumab and cetuximab in head and neck patients show encouraging survival data in both subgroups of IO-naïve and IO-pretreated SCCHN patients

On November 12, 2018 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH), reported exploratory subgroup analyses and preliminary translational data from the Phase II trial evaluating the combination of monalizumab and cetuximab (anti-EGFR) in previously treated patients with recurrent and/or metastatic squamous cell carcinoma of the head & neck (R/M SCCHN) (Press release, Innate Pharma, NOV 9, 2018, View Source [SID1234531226]). Monalizumab is a first-in-class checkpoint inhibitor targeting NKG2A inhibitory receptors expressed on tumor-infiltrating cytotoxic CD8 T lymphocytes and NK cells.

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"The subgroup analysis revealed very interesting durable responses in both IO-naïve and IO-pretreated patients," commented Pierre Dodion, Chief Medical Officer of Innate Pharma. "Patients who have failed on IO-therapy currently have no other treatment option. The fact that they appear to benefit with prolonged survival is rather remarkable and prompted us to advance our clinical program. Discussions are taking place in parallel with regards to the next steps in IO naïve patients".

"The high disease control rate that we observed in this study along with the favorable trends in progression-free and overall survival, including a preliminary estimate of median overall survival of 10.3 months, are very encouraging," commented Professor Roger B. Cohen, Principal Investigator of the study. "We also saw evidence of clinical activity in both IO-naive and IO-pretreated patients. If confirmed, these data would provide support for a highly novel immunotherapeutic combination with a unique mechanism of action for the treatment of patients with head & neck cancer."

Data from the cohort of 40 patients were reported at 2018 ESMO (Free ESMO Whitepaper) congress in October. Exploratory subgroup analysis revealed encouraging responses, durability of response, PFS and OS in IO-naïve and IO-pretreated patients.

Cut-off August 31, 2018

All patients

(n=40)

IO-naïve

(n=23)

IO-pretreated

(n=17)

ORR [95% CI]

27.5% [16-43]

35% [19-55]

18% [6-41]

Median PFS [95% CI]

5.0 m [3.7-6.9]

4.0 m[3.7-10.6]

5.0 m [3.5-NR]

Median OS [95% CI]

10.3 m [7.3-NR]

10.3 m [7.2-NR]

12.8 m [6.0-NR]

DCR 24 weeks

35% [22-51]

39% [22-59]

29% [13-53]

Median time to response [range]

1.6 m [1.5-3.9]

1.7 m [1.5-3.9]

1.6 m [1.6-3.1]

Median duration of response [95% CI]

5.6 m [3.8-NR]

5.3 m [3.8-NR]

5.6 m [3.7-NR]

Eric Vivier, Chief Scientific Officer of Innate Pharma, said: "We are combining the use of state-of-the-art technologies including high-dimensional flow cytometry, single cell RNA seq and computational pathology, to monitor the immune response in patients. Data support the mode of action of monalizumab as unleashing a multilayered immune response involving both NK and T cells. As such, monalizumab appears as a first-in-class second generation immune checkpoint inhibitor with a large spectrum of immune targets. He added: "While preliminary, translational results suggest that the combination of monalizumab and cetuximab is associated with a reshaping of "cold tumors" into "hot tumors" prone to sustain tumor immunity".

Preliminary biomarker analysis show indeed that while the combination did not impair the distribution or absolute counts of peripheral NKG2A+ NK and CD8+ T cells, an infiltration of NK cells and CD8+T cells is detected very early upon treatment (day 15) at the tumor bed. Further, tumor-infiltrating NK and CD8+ T cells may be predictive of RECIST response, tumor reduction and PFS.

Importantly, the activity of the monalizumab and cetuximab combination appears to occur across HPV status, tumor burden and PD-L1 expression.

OncoMed Announces Early Clinical Data for anti-TIGIT Antibody

On November 9, 2018 OncoMed Pharmaceuticals, Inc. (NASDAQ: OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, reported initial results from the Phase 1a dose escalation portion of a Phase 1a/b trial of etigilimab, the company’s anti-TIGIT antibody (Press release, OncoMed, NOV 9, 2018, View Source [SID1234531219]). TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is a next generation checkpoint receptor shown to block T-cell activation and the body’s natural anti-cancer immune response. OncoMed’s anti-TIGIT checkpoint inhibitor candidate is an IgG1 monoclonal antibody which binds to the human TIGIT receptor on T-cells with a goal of improving the activation and effectiveness of T-cell and NK cell tumor-killing activity. The data were presented today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting taking place in Washington, D.C.

The initial results from the Phase 1a dose escalation portion of the Phase 1a/b trial included data from 18 patients with a variety of late stage metastatic cancers including colorectal, endometrial, pancreatic, among others, who were treated with etigilimab at doses ranging from 0.3 to 20 mg/kg every other week. There were no dose-limiting toxicities through the 20 mg/kg every other week dose. In this "all comers" difficult-to-treat patient population, stable disease was observed in 7 (38.9%) patients with prolonged disease control seen in some patients with the longest durations of stable disease being 205 and 225 days. Of the remaining 11 patients in the study, ten patients had progressive disease, and one patient did not meet criteria to be evaluated for efficacy. The most frequent treatment-related adverse events were rash (27.8%), fatigue (16.7%), nausea (16.7%), pruritus (16.7%), and cough (11.1%). Immune-related adverse events, signaling immune activation included rash (27.8%), pruritus (16.7%), autoimmune hepatitis (5.6%) and stomatitis (5.6%). Grade 3 or higher treatment-related AEs included rash (16.7%), and abdominal pain, embolism, hypertension, and pulmonary embolism (11.1% each).

Biomarker analysis demonstrated a significant reduction of peripheral T regulatory cells (Tregs), most significant at doses ≥ 10 mg/kg, and signals of immune activation. These results are consistent with preclinical studies with a surrogate anti-TIGIT antibody and suggest select immune cell depletion and activation of T cell signaling in patients treated with the drug.

"These data indicate that etigilimab was well-tolerated by patients and showed modulation of specific subsets of peripheral T cells," said John Lewicki, Ph.D., President and Chief Executive Officer of OncoMed. "The decrease in peripheral Tregs and observations of stable disease in certain patients are consistent with the expected mechanisms of our IgG1 anti-TIGIT antibody."

The company is currently enrolling a single agent Phase 1a expansion cohort in select tumor types. Concurrently, the company is also enrolling the phase 1b portion of the trial where escalating doses of etigilimab are given in combination with nivolumab in the treatment of patients with solid tumors who have progressed after treatment with anti-PD1 or anti-PD-L1. The trial will define a dosing regimen that could provide the basis for expanded studies of etigilimab in combination with anti-PD1.

About TIGIT
TIGIT and its ligands, PVR and PVR-L2 comprise a novel immune checkpoint which blocks T-cells from attacking tumor cells and is similar in structure and function to the inhibitory protein PD-1. OncoMed’s anti-TIGIT antibody (etigilimab) is intended to activate the immune system through multiple mechanisms and to enable anti-tumor activity. At the 2018 AACR (Free AACR Whitepaper) Annual Meeting, OncoMed presented preclinical data (Abstract 5627) which demonstrated that anti-TIGIT treatment reduced the abundance of Tregs within tumors in animal models. Mechanistic studies demonstrated an important contribution of effector function for anti-tumor efficacy. Using a surrogate anti-TIGIT antibody, potent single-agent dose-dependent anti-tumor efficacy was demonstrated on large established CT26 WT tumors and in other models. Anti-TIGIT efficacy was shown to require effector function for tumor growth inhibition and biomarker analysis demonstrated reduction of Treg frequency and activation of T-cells and NK cells as part of the mechanism of action of anti-TIGIT. Additionally in a human tissue study, TIGIT expression on Tregs was found to be considerably higher than on CD8+ T-cells in multiplexed IHC panels across a panel of multiple solid tumors types. This program is part of OncoMed’s collaboration with Celgene.

Cerus to Present at the 2018 Canaccord Genuity Medical Technologies & Diagnostics Forum

On November 9, 2018 Cerus Corporation (Nasdaq:CERS) reported that William ‘Obi’ Greenman, Cerus’ president and chief executive officer, and Vivek Jayaraman, Cerus’ chief commercial officer, are scheduled to present a corporate update at the 2018 Canaccord Genuity Medical Technologies and Diagnostics Forum at 1:30 p.m. ET on Thursday, November 15, 2018 (Press release, Cerus, NOV 9, 2018, View Source;Diagnostics-Forum/default.aspx [SID1234531218]).

A live webcast of the presentation will be available from the Investor Relations page of the Cerus web site at View Source A replay will be available for approximately two weeks following the completion of the

Medtronic to Announce Financial Results for Its Second Quarter of Fiscal Year 2019

On November 9, 2018 Medtronic plc (NYSE:MDT) reported that it will report financial results for the second quarter of fiscal year 2019 on Tuesday, November 20, 2018. A news release will be issued at approximately 5:45 a.m. Central Standard Time (CST) and will be available at View Source The news release will include summary financial information for the company’s second quarter of fiscal year 2019, which ended on Friday, October 26, 2018.

Medtronic will host a webcast at 7:00 a.m. CST to discuss financial results for its second quarter of fiscal year 2019. The webcast can be accessed at View Source on November 20, 2018.

Within 24 hours of the webcast, a replay and transcript of the prepared remarks will be available by clicking on the Investor Events link at View Source.

Looking ahead, Medtronic plans to report its fiscal year 2019 third and fourth quarter financial results on Tuesday, February 19, 2019, and Thursday, May 23, 2019, respectively. Medtronic plans to report its fiscal year 2020 first quarter on Tuesday, August 20, 2019. Confirmation and additional details will be provided closer to the specific event.

Innovent Presents Clinical Data of Anti-PD-1 Antibody Sintilimab in Patients with First-line Squamous NSCLC at Asia Conference on Lung Cancer 2018

On November 9, 2018 Innovent Biologics, Inc. (Innovent) (HKEX: 1801), a world-class China-based biopharmaceutical company that develops and commercializes high quality drugs, reported its clinical research data on cohort E from a Phase Ib clinical trial at the International Association for the Study of Lung Cancer (IASLC) Asia Conference on Lung Cancer 2018 (#ACLC18) (Press release, Innovent Biologics, NOV 9, 2018, View Source [SID1234531216]). In this cohort of the Phase Ib clinical trial (NCT02937116), patients with first-line squamous non-small cell lung cancer (sNSCLC) were treated with sintilimab, a fully human anti-programmed cell death 1 (PD-1) monoclonal antibody, in combination with gemcitabine and cisplatin.

The combination demonstrated an objective response rate (ORR) of 64.7% and disease control rate (DCR) of 100.0%, based on data from 17 patients with at least one radiological assessment among a total of 20 patients in this cohort. As of the data analysis cutoff on September 1, 2018, after median follow up of 6.6 months, the data of median duration of response (DOR) and median progression free survival (PFS) were not yet mature, the preliminary results of which were 6.0 months and 6.8 months, respectively. Twelve-month overall survival (OS) was 87.0%. The study shows evidence of anti-tumor efficacy and an acceptable safety profile.

Based on the efficacy and safety profile from this early phase clinical trial, we have initiated ORIENT-12, a randomized, double-blinded, multicenter, phase III study of sintilimab versus placebo, both in combination with gemcitabine and platinum-based chemotherapy as first-line treatment for advanced or recurrent sNSCLC in China. Patient recruitment for this study is currently under way and Innovent plans to enroll 348 patients. The first patient dosing has been accomplished recently.

"Immune checkpoint inhibitor has brought hope to patients suffering from squamous non-small cell lung cancer, who are unfit for either target therapy due to its lack of driving gene mutation, or anti-angiogenic therapy in first line setting," said Professor Kejing Ying from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. She expressed her great expectation for the result from phase III clinical trial and the approval of sintilimab as first-line treatment for NSCLC.

"Lung cancer has the highest morbidity and mortality among malignant tumors in China. Despite breakthrough in recent years, treatment for squamous lung cancer is still limited, and the effect is unsatisfying," said Michael Yu, Founder, Chief Executive Officer and Chairman of Innovent, "At present, Innovent has launched phase III clinical study of squamous lung cancer. We hope these clinical trials will benefit squamous lung cancer patients as quickly as possible, bringing patients and their families hope for extended vitality."

About advanced or metastatic squamous non-small cell lung cancer (sNSCLC)

Lung cancer has the highest incidence and mortality among all malignancies in China. NSCLC accounts for about 80% to 85% of all lung cancer cases, and about 70% of NSCLC patients have locally advanced or metastatic disease at first diagnosis. In addition, many patients with early-stage NSCLC after undergoing potentially curative surgery eventually die from disease progression after disease recurrence or distant metastasis. Squamous NSCLC (sNSCLC) accounts for about 30% of all NSCLC patients in China. Due to its unique epidemiological, histological and molecular biological character, sNSCLC still lacks effective treatment modality, with platinum-based chemotherapy as the first-line treatment. However, platinum-based chemotherapy only obtains an objective response rate (ORR) of 30%, progression free survival (PFS) of 5.5 months and overall survival (OS) of 10.8 months, which is far from satisfying. The unmet medical needs in this patient population are high.

About ORIENT-12

ORIENT-12 is a randomized, double-blinded, multicenter, phase III study of sintilimab versus placebo, both in combination with gemcitabine and platinum-based chemotherapy as first-line treatment for advanced or recurrent sNSCLC in China. Patient recruitment for this study is currently under way and Innovent plans to enroll 348 patients. The first patient dosing has been accomplished recently.

About Sintilimab

Sintilimab is a fully human anti-PD-1 antibody. It binds to the PD-1 receptor on T cells, blocking the PD-L1 ligand from interacting with PD-1 to help restore T-cell response and immune response, thus destroying the tumor cells. Sintilimab is an anti-PD-1 monoclonal antibody jointly developed by Innovent and Eli Lilly and Company in China. National Medical Products Administration (NMPA, successor to CFDA) accepted the New Drug Application (NDA) submitted by Innovent for sintilimab on April 16, 2018, and granted it priority review status on April 23, 2018. The indication for the first new drug application is relapsed/refractory classical Hodgkin’s Lymphoma.