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Peregrine Pharmaceuticals Presents Preliminary Correlative Analysis of PD-L1 Expression from SUNRISE Trial at ASCO 2017

On June 5, 2017 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by advancing its proprietary R&D pipeline and manufacturing high quality products for biotechnology and pharmaceutical companies, reported the presentation of promising new data from its Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, Peregrine Pharmaceuticals, JUN 5, 2017, View Source [SID1234519407]). Presented results demonstrated that patients in the study’s bavituximab treatment arm who had low baseline PD-L1 expression levels had a statistically significant improvement in median overall survival (mOS) as compared to patients in the same treatment arm who had higher baseline levels of PD-L1. Data were presented by Peregrine scientists at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), being held June 2 – 6, 2017 in Chicago.

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Data presented demonstrated that patients in the study’s docetaxel plus bavituximab (D+B) treatment arm with a pre-treatment PD-L1 expression level on tumor cells of < 1% (TC0) had a mOS of 12.1 months compared to a mOS of 6.1 months for patients with PD-L1 expression ≥1% (TC1/2/3) (HR = 0.42 p=0.007). There was no difference in mOS based on PD-L1 expression levels observed in the study’s docetaxel plus placebo (D+P) control arm (10.7 months for TC0 vs. 11.1 months for TC1/2/3; HR = 0.87; p=0.609).

"We believe that these latest observations from the SUNRISE trial further support the hypothesis that bavituximab, through its immune modulating mechanism, may have more effect on tumors without pre-existent immunity. These ‘cold’ tumors suppress normal anti-tumor immune response and are categorized by very low to no PD-L1 expression on tumor cells," said Joseph Shan, vice president of clinical and regulatory affairs at Peregrine. "These latest findings, along with other recently announced clinical and preclinical data from our PS-targeting program, inform our clinical development strategy going forward and provide additional rationale for combining bavituximab with checkpoint inhibitors."

As part of the SUNRISE clinical study protocol, researchers requested but did not require that patients provide a tumor tissue sample at the time of diagnosis. In total, tissue samples were collected from 129 of the trial’s 597 patients and were assessed retrospectively for baseline PD-L1 expression levels on tumor cells. Of the 129 tissue samples collected, 122 were evaluable for PD-L1 expression on tumor cells (54 in D+B arm and 68 in D+P control arm). Of the evaluable samples in the D+B arm, 69% demonstrated PD-L1 expression levels < 1%, as compared to 59% in the D+P arm.

Bavituximab is an investigational immune-modulatory monoclonal antibody that targets phosphatidylserine (PS). PS inhibits the ability of immune cells to recognize and fight tumors. Bavituximab is believed to reverse PS-mediated immunosuppression by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. PS-targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses.

Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes grants awarded by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. These trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center (MSK) with the goal of evaluating combinations of PS targeting antibodies with checkpoint inhibitors and other immune stimulatory agents. Peregrine’s intent behind this strategy is to focus its research and development spending to further validate bavituximab’s combination potential as the company seeks to advance the program though a pharmaceutical or biotechnology partner.

Onconova Therapeutics Announces Positive Phase 2 Data in Rigosertib Treated Patients with Second-line Myelodysplastic Syndromes at the American Society of Clinical Oncology Annual Meeting

On June 5, 2017 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported the results of a Phase 2 study with rigosertib as a treatment for higher risk (HR-MDS) after failure of hypomethylating agents (HMAs) (Press release, Onconova, JUN 5, 2017, View Source [SID1234519406]). The study sought to evaluate bone marrow blast (BMBL) response to rigosertib as a surrogate for overall survival (OS) in this patient population. The results showed treatment with rigosertib resulted in a reduction in BMBL count, including complete bone marrow responses, confirming findings in earlier studies. Thus, BMBL response to rigosertib is a potential surrogate marker for improvement in overall survival in this patient population.

"In this new study for HR-MDS patients after failure of HMA therapy, we are excited to confirm a correlation between blast reduction and prolongation of survival in rigosertib treated patients. These results build upon our previous findings in the ONTIME trial showing improvement in overall survival in patients with the highest risk prognostic categories after failure of HMA treatment (ASH 2014 presentation),"said Ramesh Kumar, Ph.D., President and CEO of Onconova.

Rigosertib is currently being tested in a randomized, global, Phase 3 INSPIRE trial for this patient population.

Study Name: Relationship of Bone Marrow Blast response to Overall Survival in a Multicenter Study of Rigosertib in Patients with Myelodysplastic Syndromes with Excess Blasts Progressing on or After Treatment with a Hypomethylating Agent

Summary of Data from the 04-24 Trial

Patient Demographics:

64 patients treated, with a median age of 73, median prior HMA duration of 10.8 months.
Eligible patients had 5%-30% BMBL confirmed within six weeks pre-study and disease. progression as per International Working Group (IWG) 2006 criteria, Cheson et al., Blood 2006) on or after HMAs within two years.
Safety/Tolerability:

Intravenous rigosertib has been well tolerated to date.
More than 1,100 patients have been treated with rigosertib.
Adverse events in study 04-24 were similar to those observed in the preceding Phase 3 ONTIME Study
Objectives:

Primary Efficacy: Evaluate the relationship between BMBL response and OS in MDS patients with excess blasts (5-30%) progressing on or after treatment with azacitidine or decitabine who are administered 72-hr continuous intravenous (IV) infusions of 1800 mg/24 hour rigosertib every 2 weeks for 8 cycles and every 4 weeks thereafter. BMBL response is defined according to the International Working Group (IWG) 2006 criteria; or stable BM response (no progression),
Secondary Efficacy: Evaluate the following parameters: Overall response (CR, partial response/remission [PR], BMCR, and stable disease [SD]) according to 2006 IWG criteria; Population pharmacokinetics.
Safety: safety and tolerability of rigosertib administered as 72-hour continuous IV (5%-30% BMBL) progressing on or after treatment with azacitidine or decitabine.
Trial Design:

Phase 2 open-label, multi-center multi-national study (approximately 30-40 Centers in the US and Europe) of the efficacy and safety of Rigosertib administered as 72-hour continuous intravenous infusions in patients with myelodysplastic syndromes with excess blasts progressing on or after treatment with azacitidine or decitabine.
Treatment will continue until IWG 2006 progression criteria are met (ie, 50% increase of BMBL or worsening of cytopenias) or until death from any cause, whichever comes first.
Following these results, all patients will be followed until death and/or progression, even if they have discontinued treatment for any reason. View the complete study poster HERE.

NewLink Genetics’ Indoximod + PROVENGE® Results in Statistically Significant Improvement in Radiographic Progression-Free Survival (rPFS) for Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC) in Phase 2 Trial

On June 5, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the presentation of results from a randomized Phase 2 investigator initiated study with indoximod in combination with the therapeutic cancer vaccine, PROVENGE (sipuleucel-T), for patients with metastatic castration resistant prostate cancer (Press release, NewLink Genetics, JUN 5, 2017, View Source [SID1234519404]). The abstract, titled A phase 2 randomized, double-blind study of sipuleucel-T followed by IDO pathway inhibitor, indoximod, or placebo in the treatment of patients with metastatic castration resistant prostate cancer (mCRPC), is being presented in a poster session by Gautam G. Jha, M.D., Adjunct Assistant Professor, Division of Hematology and Oncology, University of Minnesota, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, IL this morning from 8:00-11:30 a.m. CT.

In the study, forty-six patients were randomized into two arms to receive either twice daily oral indoximod (n=22) or placebo (n=24) for 6 months beginning the day after the third and final PROVENGE infusion. The indoximod treatment arm for the study showed a statistically significant improvement in radiographic progression-free survival (rPFS) when compared to placebo and was well tolerated.

Key findings presented from the study include:

Statistically significant improvement in median rPFS was 10.3 months in the treatment arm compared to 4.1 months in the placebo arm (p = 0.011)
Median Overall Survival (OS) has not yet been reached
Patients tolerated therapy with indoximod with no significant differences in adverse events between the two arms
There was no statistical difference in the primary endpoint of ELISPOT assay immune response to PA2024, the PROVENGE-related fusion protein, in the 35 of 46 patients who had clinical samples available for testing
"Given that PROVENGE alone has not shown any PFS benefit in multiple prior studies, this randomized, placebo controlled data, although limited in number of patients, is quite encouraging and has the potential to offer some measurable clinical benefits for patients," said Dr. Jha, principal investigator of this study.

An infographic accompanying this release is available at View Source

Data reported at ASCO (Free ASCO Whitepaper) 2017 indicate that treatment with NewLink Genetics’ proprietary IDO pathway inhibitor, indoximod, post PROVENGE therapy leads to significant improvement in rPFS when compared to placebo and is well tolerated.

"These results are additional evidence that indoximod has the potential to improve outcomes for patients in combination with therapies beyond the established checkpoint inhibitors," said Charles J. Link, Jr. M.D., Chairman and CEO of NewLink Genetics.

Nektar Presents New Clinical Data from Two Studies of NKTR-214, a CD122-Biased Agonist, at 2017 American Society of Clinical Oncology (ASCO) Annual Meeting

On June 5, 2017 Nektar Therapeutics (Nasdaq: NKTR) reported that it presented new findings from two Phase 1 clinical studies of NKTR-214, Nektar’s lead immuno-oncology candidate, a CD122-biased agonist, at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Nektar Therapeutics, JUN 5, 2017, View Source [SID1234519403]).

NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting CD8+ effector T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of PD-1 on these immune cells.

"We are very excited about the initial data emerging from the PIVOT study evaluating NKTR-214 in combination with nivolumab," said Mary Tagliaferri, M.D., Senior Vice President of Clinical Development at Nektar Therapeutics. "The combination is showing early clinical benefit in patients with both melanoma and renal cell carcinoma. We’ve observed RECIST responses in 3 of 4 patients with BRAF-positive Stage IV melanoma in the study, including a durable complete response that occurred at week 6 on treatment. These patients had very poor prognosis coming into the study, including high baseline LDH levels and liver metastases. In addition, the combination treatment has a favorable safety profile and we have not observed any grade 3 or higher treatment-related AEs to-date. We look forward to identifying a Phase 2 dose and initiating the expansion cohorts for the PIVOT trial in our 8 target indications in the third quarter of 2017."

New findings were presented in patients from an ongoing Phase 1 dose-escalation study evaluating monotherapy NKTR-214 in patients with solid tumors in a poster session at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago:

Confirmed partial responses (PRs) were observed in 3 of 4 patients with Stage IV renal cell carcinoma (RCC) who were immuno-oncology (I-O) treatment naïve who experienced stable disease (SD) with tumor shrinkage while on NKTR-214 monotherapy (range of 3-8 cycles) and then received sequential therapy with nivolumab. All three patients with confirmed PRs experienced rapid responses at first 8-week scan after initiating sequential therapy with nivolumab. The fourth patient experienced SD at first 8-week scan. All four patients had progressed on one or more prior tyrosine-kinase inhibitor (TKI) therapies and all are continuing on therapy with nivolumab.
Two heavily pre-treated Stage IV patients are continuing treatment with monotherapy NKTR-214. One patient with BRAF-mutated melanoma, who was previously treated with ipilimumab and vemurafenib, continues on NKTR-214 therapy with SD for greater than 15 months. One patient with RCC who was previously treated with high-dose IL-2 and subsequently refractory to single agent treatments with OX40 and nivolumab, continues on NKTR-214 therapy with SD for greater than 10 months.
NKTR-214 monotherapy demonstrated a favorable safety profile with no immune-related adverse events (AEs) (N=28, Stage IV patients)
Data from blood and tumor samples show that NKTR-214 increases immune cells in the blood and tumor microenvironment even in subjects who have failed multiple prior immunotherapeutic agents.
Initial data were presented from the ongoing PIVOT dose-escalation trial evaluating NKTR-214 in combination with nivolumab in patients with melanoma, renal cell carcinoma and non-small cell lung cancer. As of June 1, 2017, 20 patients were enrolled in the dose-escalation phase of the ongoing PIVOT study in a number of dose cohorts. Findings from the first patients enrolled in the ongoing study are as follows:

Clinical benefit data (evaluable scans) were available for initial patients enrolled in the trial:
Responses (RECIST 1.1) were observed in 3 of 4 patients with BRAF-mutated Stage IV melanoma (1 CR, 2 uPR). Time to response for these patients, respectively, was 6 weeks, 7 weeks and 20 weeks. All three patients with responses are ongoing treatment in the trial.
Two patients with RCC who were I-O naïve were evaluable for at least two scans. A confirmed PR (-39%) was observed in one of these patients (PD-L1 negative) who progressed on prior TKI therapy. Time to response was 15 weeks. The second patient, who progressed on prior bevacizumab therapy, experienced SD and is continuing on treatment.
4 additional RCC IO naïve patients were evaluable for one scan. All four had SD in their target lesions and are continuing on treatment in the study.
On treatment tumor biopsies from the PIVOT trial show robust expansion of ICOS+ CD4 and CD8 T cells with the combination of NKTR-214 and nivolumab.
All dose cohorts of NKTR-214 and nivolumab demonstrate a favorable safety profile and are well-tolerated. In the study to-date, there are no dose-limiting toxicities, no grade 3 or higher treatment-related AEs, and no immune-related AEs (such as colitis, dermatitis, pneumonitis or endocrinopathies).
The dose-escalation portion of the trial is enrolling with the last dose cohort recently initiated (NKTR-214 0.009 mg/kg q3w + nivo 360 mg q3w) in order to identify a recommended Phase 2 dose.
NKTR-214 preferentially binds to the CD122 receptor on the surface of cancer-fighting immune cells in order to stimulate their proliferation. In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment.1,2 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

MorphoSys Presents First Safety and Efficacy Data of MOR208 in Combination with Lenalidomide from a Phase 2 Study in DLBCL

On June 5, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported safety and efficacy data from an ongoing phase 2 clinical trial ("L-MIND" study) evaluating MOR208 in combination with lenalidomide in patients with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) (Press release, MorphoSys, JUN 5, 2017, View Source [SID1234519402]). DLBCL is the most common form of non-Hodgkin’s lymphoma. Data were reported during a poster presentation at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago/USA. MOR208 is an Fc-enhanced investigational antibody directed against CD19.

"We are very excited having seen the preliminary data from the first 44 patients of our ongoing phase 2 L-MIND trial. We are particularly optimistic about the level of response rates that we have seen so far, especially complete responses. For DLBCL patients who relapse after their first-line treatment, current treatment options are very limited. We are therefore exploring potential new treatment regimens with MOR208 for this difficult-to-treat patient group", commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG.

44 patients were enrolled in the study at data cut-off, 34 of whom were evaluable for efficacy assessment. Preliminary data show an objective response in 19 out of 34 patients (ORR: 56%). Complete remission was seen in 11 out of 34 patients (CR: 32%). 16 out of 19 patients in whom responses were recorded, were still on study at time of data-cut off.

No infusion-related reactions were reported for MOR208. The most frequent adverse events observed of grade 3 or higher were hematological, comprising neutropenia, thrombocytopenia, and leukopenia, seen in 32%, 9%, and 9% of patients, respectively. To date, 27% of patients required a reduction of the lenalidomide dose due to side effects. No unexpected safety-related effects were observed.

The L-MIND trial (Lenalidomide plus MOR208 in DLBCL) is a single-arm, open-label, multicenter study of MOR208 in combination with lenalidomide. The trial will enroll approximately 80 patients with relapsed or refractory DLBCL after up to three prior lines of therapy, with at least one prior therapy including an anti-CD20 targeting therapy (e.g. rituximab). Patients in the trial could not be candidates for high-dose chemotherapy or autologous stem cell transplantation. Patients enrolled in the trial had a median age of 73 years.

In addition to the preliminary data from the phase 2 L-MIND study with MOR208 and lenalidomide in R/R DLBCL, two "trial-in-progress" posters about MOR208 were presented at ASCO (Free ASCO Whitepaper) 2017 illustrating the study designs of two other ongoing clinical combination trials of MOR208: the phase 2/3 randomized, "B-MIND" study comparing MOR208 plus bendamustine vs. rituximab plus bendamustine in patients with R/R DLBCL; and the phase 2 "COSMOS" study in R/R chronic lymphocytic leukemia (CLL) patients, who had previously discontinued treatment with a Bruton tyrosine kinase (BTK) inhibitor. The COSMOS trial is currently investigating MOR208 in combination with idelalisib.

Details of the MOR208 presentations at ASCO (Free ASCO Whitepaper) 2017

Abstract #7514, poster board #276

L-MIND: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large B-cell lymphoma (R-R DLBCL) – A single-arm phase 2 study

The poster will be presented during the session, "Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia," held on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall). The results will also be highlighted during a poster discussion session about CD19 targeting therapies on June 5, 2017 (1:15 PM-2:30 PM CDT, room E354b).

Abstract #TPS7571, poster board #330b

B-MIND: MOR208 plus bendamustine (BEN) versus rituximab (RTX) plus BEN in patients with relapsed or refractory (R-R) diffuse large B-cell lymphoma (DLBCL): An open-label, randomized phase 2/3 trial

The poster will be presented in the "Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia" session on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall).

Abstract #TPS7567, poster board#328b

COSMOS: MOR208 plus idelalisib or venetoclax in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a Bruton’s tyrosine kinase inhibitor (BTKi) – A two-cohort phase 2 study

The poster will be presented in the "Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia" session on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall).

MorphoSys will hold an Investor & Analyst Event at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting on June 5, 2017, at 6:30pm CDT (June 6, 2017: 1:30am CEST). Clinical data for MorphoSys’s investigational agents MOR208 and MOR202 will be presented by clinical investigators and company representatives.

A replay and the presentation will be made available at View Source

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 (previously Xmab(R)5574) is an Fc-enhanced monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. Furthermore, MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be a crucial component for B cell receptor (BCR) signaling.
MorphoSys AG is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. A phase 2 combination trial (L-MIND study) was started in March 2016 and is designed to investigate the safety and efficacy of MOR208 in combination with lenalidomide in approximately 80 patients with relapsed/refractory DLBCL. The phase 2/3 B-MIND study was started in August 2016 and transitioned into its phase 3 pivotal part in June 2017 following a recommendation of the IDMC based on the available data from the phase 2 initial safety evaluation. The B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in relapsed/refractory DLBCL patients who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. Furthermore, in December 2016, a third phase 2 combination trial was started with MOR208 evaluating the antibody in patients with relapsed/refractory CLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib). Currently MOR208 is being studied in combination with idelalisib; a second study arm of MOR208 plus venetoclax is currently in preparation.