On June 1, 2019 Novartis reported statistically significant overall survival (OS) results for Kisqali in combination with endocrine therapy[1]. The Phase 3 MONALEESA-7 trial evaluated Kisqali plus endocrine therapy (goserelin plus either an aromatase inhibitor or tamoxifen) as initial treatment compared to endocrine therapy alone in pre- and perimenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer[1]. MONALEESA-7 overall survival results will be featured in a press briefing today, presented as a late-breaker at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract# LBA1008), and will be published in The New England Journal of Medicine.

The significant extension in survival met the early efficacy stopping criteria at a pre-specified interim analysis following 192 deaths (median OS, not reached vs. 40.9 [95% CI: 37.8-NE] months; HR=0.712 [0.535-0.948]; p=0.00973). Overall survival rates in the intent-to-treat population (n=672) at 42 months were 70.2% for Kisqali combination therapy compared to 46.0% for endocrine therapy alone. At the time of data cut-off, 35% of women taking Kisqali combination therapy were continuing the treatment. No new safety signals were observed[1]. Kisqali is not indicated for use with tamoxifen.

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"Overall survival benefit is considered the ‘gold standard’ in cancer trials but is challenging to achieve in HR+/HER2- metastatic breast cancer. MONALEESA-7 reached this important endpoint earlier than anticipated," said Sara Hurvitz, MD, Medical Director of the Jonsson Comprehensive Cancer Center Clinical Research Unit and Director of the Breast Cancer Clinical Trials Program at UCLA. "Impactful results like these ribociclib findings are what we wish for in every clinical trial, and to achieve overall survival improvement in an incurable disease, like metastatic breast cancer, is truly an outstanding advancement for patients."

Susanne Schaffert, Ph.D., CEO, Novartis Oncology, added, "Kisqali is the only CDK4/6 inhibitor to achieve statistically significant overall survival benefit in combination with endocrine therapy, and we are so proud to share these powerful data with the medical and patient community. These exciting results add to the proven efficacy and safety profile of Kisqali, solidify it as a standard of care for people living with HR+/HER2- metastatic breast cancer and inspire us to continue to reimagine medicine."

Results from subgroup analyses showed that Kisqali plus an aromatase inhibitor demonstrated a 30.0% reduced risk of death compared to an aromatase inhibitor alone (median OS not reached vs. 40.7 months [37.4-NE]; HR=0.699 [0.501-0.976]), and Kisqali plus tamoxifen demonstrated a 20.9% reduced risk of death compared to tamoxifen alone (HR=0.791 [0.454-1.377])[1]. Kisqali is not indicated for use with tamoxifen. In the MONALEESA-7 primary analysis, increase in QTcF was on average greater and equal to 10 milliseconds in people taking tamoxifen plus placebo compared those taking aromatase inhibitor and placebo[4].

"Kisqali has characteristics that make it distinct from other CDK4/6 inhibitors. For one, Kisqali shows especially strong inhibition against CDK4. In pre-clinical data, Kisqali is four- to five-fold more potent against CDK4 compared to CDK6. CDK4 is likely the dominant CDK in breast cancer and a pivotal driver of disease progression," said Jeff Engelman, MD, Global Head of Oncology Research, Novartis Institutes for BioMedical Research.

MJ DeCoteau, Executive Director of Rethink Breast Cancer, said, "Younger women living with advanced breast cancer encounter unique challenges as they face an incurable illness at the prime of their lives – they may be students, new moms or just embarking on their careers. Breast cancer is the leading cause of cancer death in women 20-59, so knowing an approved treatment has been proven to help them live longer is an outstanding advancement and provides new hope for women with this devastating disease."

About Kisqali (ribociclib)
Kisqali (ribociclib) is the CDK4/6 inhibitor with the largest body of first-line clinical trial evidence demonstrating consistent and sustained efficacy compared to endocrine therapy alone[5]. Kisqali is the only targeted therapy, including CDK4/6 inhibitors, in combination with endocrine therapy to demonstrate significantly longer overall survival compared to endocrine therapy alone as initial endocrine-based treatment for advanced breast cancer in the MONALEESA-7 trial[5]. Overall survival follow-up is ongoing for the Phase III MONALEESA-2 and MONALEESA-3 trials.

Novartis is continuing to reimagine cancer by investigating Kisqali in early breast cancer. The NATALEE study is a Phase III clinical trial of Kisqali with endocrine therapy in the adjuvant treatment of HR+/HER2- early breast cancer being conducted in collaboration with Translational Research In Oncology (TRIO)[5].

Kisqali is approved for use in more than 75 countries around the world, including the United States and European Union member states. Kisqali was initially approved by the US Food and Drug Administration (FDA) in March 2017 and by the European Commission (EC) in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial. Kisqali in combination with an aromatase inhibitor was approved for the treatment of pre-, peri- or postmenopausal women as initial endocrine based therapy, and also indicated for use in combination with fulvestrant as both first- or second-line therapy in postmenopausal women by the FDA in July 2018 and by the EC in December 2018. Regulatory filings are underway with other health authorities worldwide[5].

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals[5].

On June 1, 2019 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported results showing that circulating EBV-targeted cytotoxic T lymphocyte precursors (EBV-CTLp) could serve as a biomarker of clinical response to tab-cel (tabelecleucel) in patients with EBV-driven diseases (Press release, Atara Biotherapeutics, JUN 1, 2019, View Source [SID1234536745]). Findings were presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2019 in Chicago.

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Ten tab-cel-treated patients with EBV-associated diseases from a multicenter expanded access protocol (EAP) study were selected. In this cohort, ex-vivo analyses of circulating EBV-CTLp following administration of tab-cel showed a statistically significant correlation (p=0.038) with clinical response.

A second presentation described the design of an ongoing Phase 1b/2 clinical study of tab-cel in combination with pembrolizumab for patients with platinum-resistant or recurrent EBV-associated nasopharyngeal carcinoma (NPC). Tab-cel has been evaluated as a single agent in previous studies where evidence of radiographic response was observed in patients with chemotherapy refractory, metastatic NPC.

Abstract 2532: Correlation of circulating EBV-targeted cytotoxic T lymphocyte precursors (EBV-CTLp) and clinical response following tabelecleucel (tab-cel) infusion in patients with EBV-driven disease
Poster Presentation Date and Time: Saturday, June 1, 2019, 8:00 a.m. – 11:00 a.m. CDT
Session Title: Developmental Immunotherapy and Tumor Immunobiology
Location: Poster Board 176, Hall A, McCormick Place, South Building, Chicago, IL
Authors: Blake T. Aftab, Daniel Munson, Kevin Rasor, Philippe Foubert, Donald Tsai, Wen Kai Weng, Armin Ghobadi, Koen van Besien, Yan Sun, Minoti Hiremath, Willis Navarro, Susan Prockop
Affiliations: Atara Biotherapeutics, University of Pennsylvania, Stanford University, Washington University, Cornell University, Memorial Sloan Kettering Cancer Center

Abstract TPS6092: Tabelecleucel in combination with pembrolizumab (Pembro) in platinum-pretreated, recurrent/metastatic Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (EBV+NPC)
Poster Presentation Date and Time: Saturday, June 1, 2019, 1:15 p.m. – 4:15 p.m. CDT
Session Title: Head and Neck Cancer
Location: Poster Board 79b, Hall A, McCormick Place, South Building, Chicago, IL
Authors: Lillian L. Siu, Joshua Bauml, Douglas Adkins, A. Dimitrios Colevas, Cesar Perez, Jennifer Choe, Yang Zhang, Wen Shi, Willis Navarro, Missak Haigentz Jr, Guilherme Rabinowits, David Pfister
Affiliations: Princess Margaret Cancer Centre, Perelman School of Medicine, Washington University School of Medicine, Stanford Cancer Institute, Sylvester Comprehensive Cancer Center, Duke University, Atara Biotherapeutics, Morristown Medical Center/Atlantic Health System, Miami Cancer Institute, Memorial Sloan Kettering Cancer Center

About EBV+ NPC
Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is primarily EBV-associated. Historical median survival rates are less than one year for patients with metastatic disease. There are no approved targeted therapies for NPC available today.

On June 1, 2019 Rakuten Medical, a clinical-stage biotechnology company developing precision-targeted cancer therapies based on its proprietary Photoimmunotherapy (PIT) platform, reported positive data results from its Phase 2a study, evaluating the safety and anti-tumor activity of RM-1929 (an EGFR-targeted antibody conjugate) PIT in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC) (Press release, Rakuten Aspyrian, JUN 1, 2019, View Source [SID1234536761]). Details of its global Phase 3 study trial design were also presented.

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The Phase 2a positive data, presented during a poster presentation discussion during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago on Saturday, June 1, 2019, showed that treatment with RM-1929 PIT resulted in clinically meaningful activity in 30, heavily pre-treated patients with rHNSCC.

The overall response rate by independent review was 43 percent (95 percent CI 25.5‒62.6), including four (13 percent) complete responses and nine (30 percent) partial responses.
The median, progression-free survival was 5.2 months (95 percent CI 2.1‒5.5), and median overall survival was 9.3 months (95 percent CI 5.2‒16.9).
Treatment with RM-1929 PIT was generally well-tolerated.
Out of the 13 patients (43.3 percent) who experienced a serious adverse event, only three (10 percent) were considered treatment-related.
"Rakuten Medical is committed to addressing the unmet medical needs of patients with cancer, and we are encouraged by the Phase 2a trial data, which demonstrated clinically meaningful anti-tumor activity in patients with late-stage head and neck cancer," said Jeannie Hou, VP of Clinical Development at Rakuten Medical. "We look forward to enrolling patients in our global Phase 3 trial in head and neck cancer."

Phase 3 Trial Overview
Rakuten Medical has initiated its Phase 3, multicenter, randomized, double-arm, open-label trial of ASP-1929 (an EGFR-targeted antibody conjugate; analogous to RM-1929) PIT versus a physician’s choice of standard-of-care for locoregional rHNSCC patients who have failed after at least two lines of therapy, of which at least one line must be systemic, platinum-based chemotherapy for HNSCC.

An overview of the trial background, design and criteria was also presented at ASCO (Free ASCO Whitepaper) during a poster session. The primary endpoints of the study are progression-free survival and overall survival, with the key secondary endpoint being objective response rate. Rakuten Medical expects to enroll approximately 275 patients in the U.S., EU and Asia Pacific.

For more information about the Phase 3 clinical trial (NCT03769506), visit www.clinicaltrials.gov.

About Photoimmunotherapy
Photoimmunotherapy (PIT) is an investigational, anti-cancer treatment platform that is comprised of a drug and device combination that utilizes monoclonal antibodies conjugated to a dye (IRDye 700DX). Transient excitation of IRDye 700Dx with non-thermal red light (690 nm) is believed to result in anti-cancer activity, which is mediated by biophysical processes that may compromise the membrane integrity of cells. The requirement of targeted binding of antibody-IR700 conjugate to a specific antigen on the cell surface and subsequent illumination is believed to result in rapid and selective cell killing and tumor necrosis with minimal effects on surrounding normal tissue. PIT may also lead to the systemic induction of innate and adaptive immunity.

On June 1, 2019 ALX Oncology, a clinical-stage immuno-oncology company developing therapies to block the CD47 myeloid checkpoint mechanism, reported new results from its Phase 1 ALX148 solid tumor program at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting [Abstract #2514] (Press release, ALX Oncology, JUN 1, 2019, View Source [SID1234536777]). As of April 18, 2019, eighty-two patients with various advanced malignancies were administered ALX148 in combination with standard regimens of either trastuzumab (n=30) or pembrolizumab (n=52). Objective responses were observed in expansion cohorts for both gastric/gastroesophageal junction cancer (G/GEJ) and squamous cell carcinoma of the head and neck (HNSCC). Key results are:

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In response-evaluable patients with HER2 positive G/GEJ (n=18) whose tumors had failed prior HER2-targeted therapy, an overall response rate (ORR) of 22% and a disease control rate (DCR) of 28% were observed.
In patients with HNSCC (n=19) whose tumors had failed prior platinum therapy, an ORR of 16% and a DCR of 26% were observed. In checkpoint naïve subjects (n=10), an ORR of 30% and a DCR of 30% were observed.
ALX148 was well tolerated and the most common treatment-related adverse event in combination with trastuzumab was grade 1/2 fatigue (27%), and with pembrolizumab was grade 1/2 increased AST (15%).
Preliminary data from paired pre- and on-study tumor biopsies from combination cohorts showed a statistically significant increase in intra-tumoral macrophages following ALX148 treatment, consistent with ALX148’s mechanism of action as a myeloid checkpoint inhibitor.
"Emerging anti-tumor activity of ALX148 combined with anti-cancer antibodies supports our hypothesis that blocking CD47 with an Fc-inactive molecule can enhance the anti-cancer immune response in patients with varying solid tumor malignancies," said Sophia Randolph M.D., Ph.D., Chief Medical Officer of ALX Oncology. "With its clinical activity and consistent safety profile, ALX148 may become a new cornerstone of immune therapy. We are excited to continue evaluating its clinical benefit in populations in need of novel treatments."

About ALX148
ALX148, designed for combination therapy, is a fusion protein comprised of an engineered high affinity CD47 binding domain of SIRPα linked to an inactive Fc region of human immunoglobulin. ALX148 potently and specifically binds CD47 and blocks its interaction with SIRPα, thus inhibiting a key immune checkpoint mechanism exploited by cancer cells. In preclinical studies, ALX148 bridges innate and adaptive immunity to maximize anti-tumor response in combinations with targeted anti-cancer antibodies and checkpoint inhibitors via Fc-dependent and Fc-independent mechanisms. No adverse effects on CD47-expressing normal blood cells were seen in ALX148 preclinical studies.

The ALX148 Phase 1 clinical trial is a two-part study that evaluates the safety, pharmacokinetics, and pharmacodynamics of ALX148. Enrollment to the combination therapy portion in which ALX148 is administered with approved anti-cancer antibodies is ongoing. For more information about the Phase 1 study, please visit clinicaltrials.gov, identifier number NCT03013218.

On June 1, 2019 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical stage immuno-oncology corporation, reported that investigators shared new positive data for its DeCidE1 (DPX-Survivac with low dose Cyclophosphamide and Epacadostat) clinical trial at the 2019 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, IMV, JUN 1, 2019, View Source [SID1234536848]).

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These new data are from the ongoing Phase 1b/2 trial evaluating the safety and efficacy of IMV’s lead candidate DPX-Survivac and intermittent low-dose cyclophosphamide (CPA), with and without Incyte’s IDO1 enzyme inhibitor epacadostat, in patients with advanced recurrent ovarian cancer. New data from evaluable patients from the phase 2 monotherapy arm of the trial indicated the potential for DPX-Survivac to impact solid tumor growth in hard to treat ovarian cancer patients. Longer-term follow-up from the phase 1b portion of the trial continued to demonstrate that the levels of survivin-specific T cells in the blood of patients – a measure of DPX-Survivac’s novel mechanism of action (MOA) – correlated with durable clinical benefits.

Updated Clinical Data for DeCidE1

In a poster presentation, Janos L. Tanyi, M.D., Ph.D., Assistant Professor of Obstetrics and Gynecology at the Hospital of the University of Pennsylvania, provided an update on the clinical results from the first patients enrolled in the phase 2 monotherapy cohort. Researchers have enrolled 19 of 28 participants to date:

Of seven patients evaluable at data cut-off in the monotherapy arm, five showed signs of treatment benefits, including reduction of target lesions in two patients, while two patients progressed.

Within the group of four patients with low tumor burden – a potential predictor of response – three showed stable diseases including two reductions in tumor burden continuing the positive trend seen in earlier results.

All subjects evaluable for T cell responses (five of five) showed survivin specific T cell activation in the blood, four of five showed a robust response. IHC analysis for tumor infiltration is ongoing

Treatments have been well tolerated.

"We believe that immunotherapy can and should be an integral part of treatment options for hard-to-treat cancers, including solid tumor indications like ovarian cancer in which patients continue to maintain an urgent need for better outcomes," said Frederic Ors, Chief Executive Officer, IMV Inc. "We continue to accumulate evidence of DPX-Survivac’s clinical activity in these patients and are encouraged by the multiple tumor shrinkages and long-lasting responses we have seen to date."

The data also highlighted long-lasting responders from the phase 1b portion of the study with key takeaways as follows:

Prolonged duration of clinical benefits reaching up to more than two years, surpassing the progression-free survival to previous treatments, including platinum-based chemotherapy.

Long-lasting clinical benefits and high levels of survivin specific T cells are associated with long-term treatment;

One subject has received DPX-Survivac for more than 21 months so far. This finding is the longest duration of treatment for DPX-Survivac on record to date.

It is supportive of DPX Survivac’s ability to maintain high levels of survivin-specific T cells in the blood over a prolonged period of time.

About the DeCidE1 Phase 1b/2 Trial

The DeCidE1 study is an open label, uncontrolled phase 1b/2 trial to assess the safety and efficacy of DPX-Survivac and cyclophosphamide with and without epacadostat in individuals with advanced, platinum-sensitive and resistant ovarian cancer. IMV completed enrollment of 53 subjects in the phase 1b cohort in December 2018. Following positive top line data, IMV amended the phase 2 protocol to stop enrollment in the combination arm with epacadostat and evaluate DPX-Survivac monotherapy with CPA in patients with lower tumor burden. As of the May 27, 2019 data cut-off date, 12 subjects have been enrolled in the phase 2 randomized portion of the trial and 7 subjects have been enrolled so far in the monotherapy population with lower baseline tumour burden.

The amended phase 2 cohort of the DECIDE1 trial is targeting enrollment of at least 16 subjects in the population with a lower baseline tumor burden. Enrollment is ongoing at multiple sites in the U.S. and Canada.

About DPX-Survivac

DPX-Survivac is the lead candidate in IMV’s new class of immunotherapies that programs targeted T cells in vivo. It has demonstrated the potential for industry-leading targeted, persistent, and durable T cell activation. IMV believes this mechanism of action (MOA) is key to generating durable solid tumor regressions. DPX-Survivac consists of survivin-based peptides formulated in IMV’s proprietary DPX drug delivery platform. DPX-Survivac is designed to work by eliciting a cytotoxic T cell immune response against cancer cells presenting survivin peptides on their surface.

Survivin, recognized by the National Cancer Institute (NCI) as a promising tumor-associated antigen, is broadly over-expressed in most cancer types, and plays an essential role in antagonizing cell death, supporting tumor-associated angiogenesis, and promoting resistance to anti-cancer therapies. IMV has identified over 15 cancer indications in which the over-expression of survivin can be targeted by DPX-Survivac.

DPX-Survivac has received Fast Track designation from the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer, as well as orphan drug designation status from the U.S. FDA and the European Medicines Agency (EMA) in the ovarian cancer indication. It is currently being evaluated in multiple Phase 1b/2 clinical trials.