On June 1, 2019 Moderna, Inc., (Nasdaq: MRNA) a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported interim data from an ongoing Phase 1 clinical study in patients with both resected (adjuvant) and unresected (advanced) solid tumors (Press release, Moderna Therapeutics, JUN 1, 2019, View Source [SID1234536769]). The data showed that the Company’s mRNA personalized cancer vaccine (PCV) mRNA-4157, given alone or in combination with Merck’s pembrolizumab (KEYTRUDA), was well-tolerated at all doses tested and elicited neoantigen-specific T-cell responses. There were no vaccine-related serious adverse events (SAEs) reported for the PCV when administered to patients as a monotherapy or in combination with pembrolizumab.

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Presented today at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, the study demonstrates the immunogenicity of Moderna’s mRNA platform for developing PCVs. In addition, clinical activity was observed in some patients receiving mRNA-4157 in combination with pembrolizumab. These safety, tolerability and immunogenicity data and the initial clinical activity observed support Moderna’s randomized Phase 2 study investigating pembrolizumab in combination with a 1 mg dose of mRNA-4157, compared to pembrolizumab alone, for the treatment of high-risk adjuvant melanoma.

"We are encouraged by these interim data from our personalized cancer vaccine program, which involves designing and manufacturing a unique vaccine for each patient based on their specific tumor," said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna. "This study demonstrates the ability of Moderna’s mRNA personalized cancer vaccine to elicit T-cells that are specific to the cancer mutations. We also observed early signs of clinical activity of our personalized cancer vaccine in combination with pembrolizumab, including in two patients previously treated with checkpoint inhibitors. We look forward to building on these learnings about tolerability and immunogenicity by assessing activity in a randomized Phase 2 study for the treatment of adjuvant melanoma."

"For decades, the cancer community has been working on the concept of developing medicines that can be personalized down to the individual patient level," said Howard A. "Skip" Burris III, M.D., president, clinical operations & chief medical officer at Sarah Cannon Research Institute, and a principal investigator of the mRNA-4157 Phase 1 study. "We know that cancer mutations are rarely shared between patients, so it’s encouraging to see individualized, personalized cancer vaccines like mRNA-4157 eliciting immune responses. We’re pleased to be a part of a study that aims to advance the science of immunotherapy through mRNA vaccines, and deliver a novel approach that is customized for each patient."

About the Data

Abstract 2523: A phase 1 multicenter study to assess the safety, tolerability and immunogenicity of mRNA-4157 alone in patients with resected solid tumors and in combination with pembrolizumab in patients with unresectable solid tumors.

Presented by: Howard A. Burris, M.D., FACP, FASCO, Sarah Cannon Research Institute
(Poster Session, Saturday, June 1, 8:00 a.m. – 11:00 a.m. CT followed by a Poster Discussion at 1:15 p.m. – 2:45 p.m. CT)

The ASCO (Free ASCO Whitepaper) poster is now available on the "Events and Presentations" section of our website.

In this dose-escalation study, 13 patients with resected solid tumors (melanoma, colon and lung cancers) received mRNA-4157 as adjuvant monotherapy after resection of their primary tumor. An additional 20 patients with metastatic, unresected solid tumors (melanoma, bladder, lung, colon, prostate, head and neck and endometrial cancers) received at least one dose of mRNA-4157 in combination with pembrolizumab.

Results:

mRNA-4157 was well-tolerated at all dose levels studied with no dose-limiting toxicities or grade 3/4 adverse events (AEs) or SAEs reported when administered as a monotherapy or in combination with pembrolizumab. The most common grade 2 adverse events were fatigue, soreness at the injection site, colitis and myalgias.
A cohort of patients at the top dose level (1 mg) are undergoing apheresis and deeper characterization of immunogenicity responses. Data from one such patient was available at the data cutoff and showed neoantigen-specific CD8 T-cell responses were detected to 10 out of 18 class I neoantigens after the 4th dose of the vaccine (compared to 0/18 at baseline).
Clinical responses (one complete response + five partial responses) at doses ranging from 0.04-1.0 mg were observed in 6 out of 20 patients receiving at least one dose of mRNA-4157 in combination with pembrolizumab. The complete response occurred to pembrolizumab monotherapy before mRNA-4157 was administered. Of the five partial responses, two were seen in patients previously treated with a checkpoint inhibitor.
Of the 13 patients who received adjuvant mRNA-4157 monotherapy, all patients have completed a full course of vaccination per the study protocol. Eleven patients remained disease free up to 75 weeks on study.
Additionally, the National Cancer Institute (NCI) presented early data today from its Phase 1 study of PCV mRNA-4650 as a monotherapy for patients with advanced metastatic cancers. The NCI program uses Moderna’s mRNA technology but uses a different neoantigen selection process and study design than Moderna’s Phase 1 mRNA-4157 study.

Abstract 2643: A Phase 1/2 study to assess the immunogenicity and tolerability of personalized mRNA vaccine mRNA-4650 encoding defined neoantigens expressed by the autologous cancer.

Presented by: Gal Cafri, Ph.D., Postdoctoral Fellow, National Cancer Institute Surgery Branch
(Poster Session, Saturday, June 1, 8:00 a.m. – 11:00 a.m. CT)

Conference Call

Moderna will host a conference call and webcast on Monday, June 3 at 8:00 a.m. ET to discuss these mRNA-4157 data. Participants are invited to listen by dialing (866) 922-5184 (domestic) or (409) 937-8950 (international) and providing conference ID 3016438 or join the live webcast by going to the "Events and Presentations" area on the Investors page of the Company’s website, www.modernatx.com. An archived webcast of the conference call can also be accessed through the Company’s website and a replay of the call will be available there for four weeks after the call.

About Moderna’s Immuno-Oncology Programs

Moderna’s oncology programs are currently focused on two main areas: cancer vaccines and intratumoral immuno-oncology (I/O) therapies. Moderna is developing these potential mRNA treatments as monotherapies and/or in combination with checkpoint inhibitors from our strategic collaborators Merck and AstraZeneca. The company currently has five I/O programs in development, including two programs advancing into Phase 2 trials.

An advantage of Moderna’s mRNA platform is that it allows for investigational medicines that combine in a single mRNA therapy several different approaches to activate the immune system to attack cancer, either with mRNA encoding for common tumor proteins found across cancer types or multiple mRNAs encoding for various immunomodulatory proteins.

Moderna’s investigational PCVs are designed to use neoantigens identified from an individual’s tumor to program the body’s immune system to elicit a more effective anti-tumor response. Upon sequencing the tumor, Moderna’s proprietary algorithms predict the neoantigens (antigens encoded by tumor-specific mutated genes) most likely to trigger the immune system to attack a particular cancer. Today, mRNA encoding up to 34 unique neoantigens can be delivered in a single vaccine. Moderna develops and manufactures these investigational PCVs at its personalized vaccines unit within its Norwood, Mass. manufacturing facility.

On June 1, 2019 Kymab, a clinical-stage biopharmaceutical company developing antibody-based therapeutics, reported a poster presentation detailing updates on the ongoing clinical trial of the company’s anti-ICOS program KY1044 at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Kymab, JUN 1, 2019, View Source [SID1234537016]). The poster details the first-in-human clinical study (NCT03829501) of KY1044, Kymab’s fully human anti-ICOS IgG1 antibody. KY1044 is designed to both deplete intratumoral regulatory T cells and stimulate effector T cells to promote the immune response against tumors. The study was initiated in February of this year.

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Title: A first-in-human study of KY1044, a fully human anti-ICOS IgG1 antibody as monotherapy and in combination with atezolizumab in patients with selected advanced malignancies.

Presenter: Sonia Quaratino M.D. Ph.D., Chief Medical Officer, Kymab

Abstract #: TPS2644

Session Title: Developmental Immunotherapy and Tumor Immunobiology

Location: Hall A

Poster board #: 288a

Date and Time: Saturday June 1, 8:00 – 11:00 a.m. CT

"We are incredibly excited to be underway with our lead immune oncology program, which has shown very encouraging results in preclinical cancer models," said Sonia Quaratino, M.D., Ph.D., Chief Medical Officer of Kymab. "We look forward to the data that will be generated from these first studies exploring the potential synergy of our programs for the benefit of patients with advanced solid cancer."

The abstracts have been published on the ASCO (Free ASCO Whitepaper) website, and may be accessed via View Source

###ENDS###

Notes to Editors
Read the PDF version of the official release.

About the Study
NCT03829501 is a Phase 1/2, open label, multi-center study to evaluate the safety, efficacy and tolerability of KY1044 as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies. The dose escalation of KY1044 as a single agent commenced in February 2019.

For more information visit www.clinicaltrials.gov.

About KY1044
KY1044 is a fully human monoclonal antibody discovered by Kymab’s IntelliSelect Transgenics platforms. KY1044 has now been tested in a number of highly illustrative syngeneic models, in which KY1044 was observed to strongly inhibit tumor growth in cancers both as a monotherapy and in combination with other immunotherapies.

Inducible T Cell Co Stimulator (ICOS), is expressed upon activation on T cells and at high levels on the majority of FOXP3+ regulatory CD4+ T cells. Available data suggest that depletion of these immunosuppressive cells from the tumor microenvironment may enhance the patient’s anti-tumor immune response.

On June 1, 2019 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported monotherapy data from the dose escalation portion of the Phase 1a/1b clinical trial of FPA150 in patients with advanced solid tumors (Press release, Five Prime Therapeutics, JUN 1, 2019, View Source [SID1234536770]). These data were presented at the Developmental Immunotherapy and Tumor Immunobiology Poster Session during the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster can be found on the Scientific Publications page of the Five Prime Therapeutics website.

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The data are the first presentation of FPA150 results and include safety and pharmacokinetics results from the Phase 1a monotherapy dose escalation portion of the study. The Phase 1a monotherapy portion of the study is being conducted in patients with advanced solid tumors, and the Phase 1b monotherapy expansion is enrolling patients with breast, ovarian and endometrial tumors that overexpress B7-H4.

"FPA150 is a first-in-class B7-H4 antibody that blocks inhibitory signaling to CD8 T cells and promotes the killing of B7-H4 overexpressing tumors through enhanced ADCC," said Jasgit Sachdev, M.D. and Director of Breast and Gynecologic Early Phase Trials at the HonorHealth Research Institute. "It is promising to see in this study that FPA150 was well tolerated at doses as high as 20mg/kg with no dose-limiting toxicities."

The open-label, multi-dose, multi-center Phase 1a dose escalation study was conducted in patients with advanced-stage solid tumors regardless of B7-H4 overexpression at monotherapy doses ranging from 0.01 to 20 mg/kg every three weeks in an accelerated titration followed by 3+3 design and in a separate dose exploration cohort in which patients with tumors that overexpress B7-H4 were treated at doses of 3 or 10 mg/kg every three weeks with mandatory pre- and on-treatment biopsies.

FPA150 monotherapy demonstrated a favorable safety profile with no dose-limiting toxicities or treatment-related serious adverse events. Evaluation of anti-tumor activity is ongoing. A recommended dose of 20 mg/kg every three weeks was selected based on safety and pharmacokinetics.

"Rapid enrollment of this first-in-human study of a novel targeted agent with checkpoint blockade and ADCC activity highlights the significant unmet need in patients with advanced breast and gynecologic cancers," said Helen Collins, Chief Medical Officer of Five Prime Therapeutics. "The preliminary data from the Phase 1a portion of this study, in patients with tumors overexpressing B7-H4, support continued evaluation of FPA150 in the monotherapy and in the anti-PD1 combination therapy setting."

Of the 29 patients in the Phase 1a portion of the study,18 had B7-H4 positive tumors based on medium or high immunohistochemistry (IHC) scores, including 11 patients with advanced ovarian cancer. Of these, one patient with ovarian cancer, who had been treated with seven prior lines of therapy including anti-PD1 therapy, achieved a confirmed partial response with a duration of 6.2 months.

Monotherapy Phase 1b expansion began in February 2019 and is enrolling cohorts of patients with B7-H4 positive breast, ovarian and endometrial cancers at a dose of 20 mg/kg every three weeks. A safety lead-in of the combination of Keytruda (pembrolizumab), a PD1 antibody, and FPA150 has also begun enrolling patients with B7-H4 positive ovarian cancer. The company expects to present preliminary efficacy results from the monotherapy expansion cohorts and early safety results from the FPA150-Keytruda combination at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) in September 2019.

About FPA150
FPA150 is a novel, fully human, afucosylated monoclonal antibody targeting B7-H4. B7-H4 overexpression is observed in multiple solid tumors, including breast and gynecologic cancers. FPA150 is designed with a dual mechanism of action: blocking the T cell checkpoint activity of B7-H4 as well as promoting enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells expressing B7-H4.

About Five Prime Therapeutics
Five Prime Therapeutics, Inc. discovers and develops innovative protein therapeutics to improve the lives of patients with serious diseases. Five Prime’s product candidates have innovative mechanisms of action and address patient populations in need of better therapies. The company focuses on researching and developing immuno-oncology and targeted cancer therapies paired with companion diagnostics to identify patients who are most likely to benefit from treatment with Five Prime’s product candidates. Five Prime has entered into strategic collaborations with leading global pharmaceutical companies and has promising product candidates in clinical and preclinical developm

On June 1, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported that biomarker and clinical data from PIVOT-02 is being presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Meeting in Chicago, Illinois (Press release, Nektar Therapeutics, JUN 1, 2019, View Source [SID1234536786]).

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New baseline biomarker analyses and updated clinical study efficacy and safety results were shared in a presentation titled, "Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab" (Abstract #2623/Poster Board #267) by Michael Hurwitz, Ph.D., M.D. who serves as Assistant Professor of Medicine, Medical Oncology at Yale Cancer Center during the "Developmental Immunotherapy and Tumor Immunobiology" poster session on Saturday, June 1, 2019.

"The Stage IV melanoma patients enrolled in the ongoing PIVOT-02 study continue to experience both deepening and durability of response over time," said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar Therapeutics. "This translated into a 34% rate of complete response at a 12-month follow-up for the 38 efficacy-evaluable patients in this cohort. Further, 42% of patients achieved a 100% reduction in target lesions. Finally, corresponding lymphocyte data highlight the benefit of replenishing and stimulating T cells continuously over the course of treatment with an I-O doublet regimen."

Bempegaldesleukin (NKTR-214, bempeg) is an investigational, CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 beta-gamma receptor. PIVOT-02 is an ongoing Phase 2 study evaluating bempeg in combination with nivolumab in solid tumors.

Highlights from the biomarker, clinical efficacy and safety data presented at ASCO (Free ASCO Whitepaper) 2019 are provided below:

Biomarkers and Mechanism of Action:

Exploratory biomarker analyses of PIVOT-02 baseline tumor biopsies identified immune signatures that potentially enrich for response in patients with 1L metastatic melanoma and not 1L metastatic urothelial carcinoma.
Notable response rates were seen in both 1L metastatic melanoma and 1L metastatic urothelial cancer patients (ASCO 2019 and ASCO (Free ASCO Whitepaper)-GU 2019), regardless of PD-L1 status or unfavorable tumor microenvironments.
12 Month Follow-Up for 1L Melanoma Cohort in PIVOT-02:
(Response measured by RECIST 1.1 by independent central radiology review for 38 efficacy-evaluable patients per protocol which were treated at the recommended Phase 2 dose in PIVOT-02 and with >1 on treatment scan. Data cut as of March 29, 2019):

At a median time of follow-up of 12.7 months, confirmed objective response rate (ORR) was 53% (20/38) in efficacy-evaluable patients, with 34% (13/38) of patients achieving confirmed complete responses. 42% (16/38) of patients achieved a maximum reduction of 100% in target lesions. DCR, also known as disease control rate (CR+ PR + SD) was 74%.
Median time to response was 2 months. Median duration of response was not reached. At the 12.7 month median follow-up, data were too immature to calculate median progression-free survival (PFS).
80% (16/20) of patients with responses have ongoing responses. Amongst the 35 patients with known pre-treatment PD-L1 status, ORR in PD-L1 negative patients was 6/14 (43%) and in PD-L1 positive patients was 13/21 (62%). One of three patients with unknown PD-L1 baseline status experienced a CR.
The most common (>30%) treatment-related adverse events (TRAEs) were grade 1-2 fatigue (65.9%), pyrexia (61.0%), rash (56.1%), pruritus (48.8%), nausea (41.5%), influenza like illness (39.0%), arthralgia (36.6%), chills (34.1%) and myalgia (31.7%). A total of 6/41 (14.6%) of patients experienced a Grade 3 (G3) or higher TRAE with 4/41 (9.8%) patients discontinuing treatment due to a TRAE. A total of 41 patients have been treated at the RP2D with 3 patients discontinuing prior to 1st scan due to an unrelated treatment-emergent adverse event (n=1) and patient decision (n=2).
A Phase 3 trial evaluating bempeg in combination with nivolumab versus nivolumab in first-line advanced melanoma patients is currently recruiting patients (NCT03635983). A Phase 2 pivotal trial evaluating bempeg in combination with nivolumab in first-line metastatic urothelial cancer is currently recruiting patients (NCT03785925).

Details of the poster presentation are provided below and a link to a copy of the poster presentation is available on Nektar’s corporate website: View Source

Abstract #2623/Poster Board #267
Title: "Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab", Hurwitz, M., et al.
Date: Saturday, June 1, 2019, 8:00 a.m. – 11:00 a.m. Central Time
Location: McCormick Place, Exhibit Hall A

On June 1, 2019 Intensity Therapeutics, Inc., a clinical-stage biotechnology company pioneering a novel, immune-based approach to treat solid tumor cancers through direct injection of its proprietary therapeutic agents, reported positive preliminary results from the company’s ongoing Phase 1/2 clinical trial of its lead product candidate, INT230-6, in a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Intensity Therapeutics, JUN 1, 2019, View Source [SID1234536755]).
The poster highlights the results of 34 patients with 15 different types of advanced or metastatic solid tumors that have failed all or are not candidates for approved, available therapies.

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INT230-6 was well tolerated in doses up to 120 mL, including intratumoral dosing into more than 100 tumors deep in the body. The 120 mL dose of INT230-6 contains amounts of the cytotoxic agents greater than a typical intravenous (IV) dose. Based on comparisons to historical IV data of the active agents comprising INT230-6, the observed pharmacokinetic profiles indicate that drug remains mostly in the tumor following INT230-6 dosing. While the trial is aimed at assessing safety, several patients have shown tumor shrinkage and prolonged disease control after completing INT230-6 treatment. The results show greater benefit in patients who have received higher doses, and who have had multiple tumors injected. Dose escalation is ongoing.

Additionally, the immune activation data observed was consistent with nonclinical data, as local delivery of INT230-6 into tumors induced an immune response with increases of CD4+ and CD8+ T-cells in the blood and in the tumor microenvironment without any immune-related adverse events. Several patients have had shrinkage of non-injected tumors indicating an abscopal response.

"We are excited and encouraged by the positive preliminary results of our Phase 1/2 trial," said Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "It is our aim to improve cancer treatment, reduce the side effects associated with systemic therapies and improve patient outcomes using intratumorally dosed INT230-6."

"The patients in our trial have a tremendous need for a new therapy. They have failed a median of three prior treatments with a number of patients having progressed following seven or more drug therapies," said Ian B. Walters, MD, Chief Medical Officer of Intensity Therapeutics. "Thus far, the data indicate that direct intratumoral injection of our product minimizes systemic side effects while promoting an augmented natural immune response that can fight a patient’s cancer for several months following completion of our treatment."

Details of the poster presentation are as follows:

Title: Safety profile of INT230-6, a novel intratumoral (IT) formulation, during injections into a variety of refractory deep and superficial tumors with evidence of tumor regression and immune activation

Abstract Number: 2602

Date/Time: Saturday, June 1, 2019, 8-11 a.m. CDT

Poster Session: Developmental Immunotherapy and Tumor Immunobiology

Presenter: Anthony El-Khoueiry, MD, Associate Professor of Clinical Medicine and Director of the Phase I Drug Development Clinical Program, University of Southern California

About INT230-6

INT230-6, Intensity’s lead proprietary product candidate, is designed for direct intratumoral injection. The drug is comprised of two proven, potent anti-cancer agents and a penetration enhancer molecule that helps disperse the drugs throughout tumors and diffuse into cancer cells. INT230-6 is being evaluated in a Phase 1/2 clinical study (NCT03058289) in patients with various advanced solid tumors. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor kill and recruitment of dendritic cells to the tumor micro-environment that induced anti-cancer T-cell activation. Treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responder animals with long-term, durable protection from multiple re-inoculations of the initial cancer and resistance to other cancers. In mouse models, INT230-6 has shown strong synergy with checkpoint blockage, including anti-PD-1 and anti-CTLA4 antibodies. INT230-6 was discovered from Intensity’s DfuseRxSM platform.