On June 5, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that treatment with rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC), demonstrated a confirmed overall response rate (ORR) of 39 percent and clinical benefit rate (stable disease or better) of 89 percent in patients with recurrent or refractory small cell lung cancer (SCLC), identified with high expression of DLL3 (Press release, AbbVie, JUN 5, 2016, View Source [SID:1234513030]). Rova-T demonstrated a one-year overall survival (OS) rate of 32 percent in the recurrent/refractory second- and third-line patient population. These new data were presented at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago and featured in the "Best of ASCO (Free ASCO Whitepaper)" program, which presents scientific and educational highlights from the meeting. Less than one percent of all data abstracts are selected for this program.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the trial, the most common treatment-emergent adverse events were fatigue (35 percent), pleural effusion (31 percent), edema peripheral (27 percent), nausea (19 percent), hypoalbuminemia (18 percent), thrombocytopenia, rash maculo-papular and decreased appetite (16 percent each). Grade three and higher severe toxicities were thrombocytopenia (11 percent), pleural effusion (8 percent), fatigue (4 percent), edema peripheral, and rash maculo-papular (3 percent each).

"These data further contribute to our understanding of the potential impact that treatment with Rova-T, a predictive biomarker-based therapy, could have on pretreated small cell lung cancer patients identified as high expressers of DLL3," said Charles M. Rudin, M.D., Ph.D., Chief of the Thoracic Oncology Service at Memorial Sloan Kettering. "The results presented at ASCO (Free ASCO Whitepaper) support further clinical development of this compound."

Small cell lung cancer (SCLC) is an aggressive, difficult-to-treat form of cancer that accounts for roughly 13-15 percent of all lung cancers.1,2 The five year survival rate for extensive-stage SCLC remains at less than 5 percent3 and there are limited treatment options available for the more than 234,000 people diagnosed with SCLC annually.1,2,4 Treatment options for patients remain limited, with chemotherapy and radiation being the most common forms of first- and second-line treatment.5

"Due to the aggressive nature of small cell lung cancer, there are limited treatment options available, resulting in a typically poor prognosis for most patients," said Mike Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "Rova-T represents a potential new approach to treating this disease by targeting DLL3, a protein that is expressed in the majority of small cell lung cancer patients. We are committed to further developing this compound and look forward to the possibility of delivering it to patients in need of new treatment options."

About the Phase 1a/1b Trial
This Phase 1a/1b, multicenter, open label, dose escalation trial was designed to assess the safety, pharmacokinetics, and preliminary efficacy of rovalpituzumab tesirine (Rova-T) as monotherapy in patients with recurrent small cell lung cancer (SCLC). The trial enrolled 74 patients, all of whom had failed at least one prior standard therapy. The primary objectives were maximum tolerated dose and an overall response rate (ORR), assessed by Response Evaluation Criteria In Solid Tumors (RECIST). Secondary objectives included pharmacokinetics and RECIST-assessed progression-free survival (PFS) and overall survival (OS). As well, the clinical benefit rate (stable disease or better) was assessed by RECIST.

About Rovalpituzumab Tesirine (Rova-T)
Rova-T is an investigational antibody-drug conjugate targeting the cancer-stem cell-associated delta-like protein 3 (DLL3)6, which is expressed in more than 80 percent of small cell lung cancer (SCLC) patient tumors, where it is prevalent on tumor cells, including cancer stem cells, but not present in healthy tissue.7 Rova-T combines a targeted antibody that delivers a cytotoxic agent directly to the DLL3-expressing cancer cells while minimizing toxicity to healthy cells. Rova-T is under investigation as a third-line treatment in SCLC.7 Studies designed to select a Rova-T regimen for first-line registration will be starting soon.8 The expression of DLL3 suggests Rova-T may be useful across multiple tumor types, including metastatic melanoma, glioblastoma multiforme and some prostate, pancreatic and colorectal cancers.7

Rova-T is an investigational compound and its efficacy and safety have not been established by the FDA or any other health authority.

On June 5, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported safety and preliminary efficacy data from a Phase 1 study of ABT-414 – an investigational antibody drug conjugate (ADC) for epidermal growth factor receptor (EGFR) amplified, recurrent glioblastoma (GBM) – showed no dose-limiting toxicities and frequent, reversible ocular toxicities (Press release, AbbVie, JUN 5, 2016, View Source [SID:1234513029]). Additionally, an estimated 30 percent (n=44) of patients treated with ABT-414 as monotherapy were progression free at six months [95% CI=17, 44] (secondary endpoint). These results, from an expansion cohort of one arm (Arm C) of a three-arm open-label study, were presented today at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago.1 Amplified EGFR is the most common genetic mutation associated with malignant GBM, an aggressive brain cancer.2

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As of January 7, 2016, the most common serious adverse event (>1 patient) (n=48) was seizure (8%). Additionally, Best Response Assessment in Neuro-Oncology (RANO) Criteria, an assessment of tumor response used in GBM, identified two partial responses, 18 patients with stable disease, and 24 with progressive disease for a total of 44 patients with complete data.1

"With standard of care therapy,3 patients with GBM, the most common and most aggressive form of brain cancer,4 have a median survival of 15 months after diagnosis and two-year survival is 30%.5 There remains an urgent unmet need for new treatment options for this devastating brain cancer," said Martin van den Bent, M.D., Ph.D., head, Neuro-Oncology Unit, Erasmus MC Cancer Institute, the Netherlands, and lead investigator of the study. "These data are important as they demonstrate the potential of ABT-414 and underscore the need for further investigation in glioblastoma."

Additional Safety Findings
Grade 3/4 treatment emergent adverse events (TEAEs) (>1 patient) were keratitis (15%), corneal epithelial microcysts (8%), hemiparesis (6%), hyperglycemia (6%), muscular weakness (6%), seizure (6%), blurred vision (4%) and ulcerative keratitis (4%).The most common TEAEs (?25% patients) in this study arm were blurred vision (60%), headache (29%), photophobia (29%), dry eye (27%), eye pain (27%), and fatigue (27%). The most common serious adverse event (>1 patient) (n=48) was seizure (8%).1

"These results suggest that ABT-414 may have important activity for certain groups of patients with glioblastoma and support the continuation of the ongoing randomized studies," said Gary Gordon, M.D., vice president, oncology clinical development, AbbVie. "AbbVie is committed to continuing to invest in technologies and approaches, including antibody drug conjugates like ABT-414, with the goal of delivering a remarkable impact on cancer treatment."

Based on these results, together with previously presented data from this study, AbbVie advanced ABT-414 to a randomized Phase 2 clinical trial in patients with EGFR-amplified GBM.1

About this Study
The Phase 1, open-label trial was designed to evaluate the safety, pharmacokinetics and maximum tolerated dose of ABT-414. Three study arms evaluated ABT-414 with radiotherapy and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) (Arm A), with TMZ in patients with newly diagnosed glioblastoma who have just completed radiation and TMZ or recurrent GBM (Arm B) or as monotherapy in patients with recurrent GBM (Arm C).1

Eligible patients in Arm C were adults with a Karnofsky Performance Status (KPS) score ?70, EGFR amplification (confirmed centrally), recurrent GBM, normal end-organ function and no prior treatment with bevacizumab. Forty-eight EGFR-amplified recurrent GBM patients were treated in this arm. The median age was 59 years (range, 35-80). Most patients had prior therapies: 40 percent had one, 48 percent had two, and 10 percent had three or more prior therapies.1

About ABT-414
ABT-414 is an investigational monoclonal antibody drug conjugate (ADC) targeting EGFR (epidermal growth factor receptor) developed by AbbVie researchers with components in-licensed from Life Science Pharmaceuticals, Inc. and Seattle Genetics.1 It is being evaluated for the treatment of patients with EGFR-amplified glioblastoma, an aggressive malignant primary brain tumor.1,4 In 2014, the FDA and the European Medicines Agency granted orphan drug designation for the treatment of glioblastoma and glioma, respectively.6,7 ABT-414 is an investigational compound and its efficacy and safety have not been established by the FDA or any other health authority.

About Glioblastoma
Glioblastoma is the most common and most aggressive type of malignant primary brain tumor.4 Mutations in EGFR are the most common genetic abnormality associated with glioblastoma, with a frequency of about 50 percent.2 Prior to diagnosis, patients may experience headache, vision problems, nausea/vomiting, personality changes and seizures.4 For adults with more aggressive glioblastoma, treated with standard therapy, median survival is about 15 months.5 Treatment for glioblastoma remains challenging.4 Standard treatment is surgical resection, radiotherapy and concomitant adjunctive chemotherapy.5

On June 5, 2016 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that Professor Martine Bagot, Head of the Dermatology Department at the Saint-Louis Hospital in Paris discussed the protocol of the ongoing first in human study of IPH4102 in patients with relapsed/refractory cutaneous T-cell lymphomas (CTCL) in a "Trial in progress" poster at the 2016 ASCO (Free ASCO Whitepaper) annual meeting (June 3-7, 2016, in Chicago, USA) (Press release, Innate Pharma, JUN 5, 2016, http://innate-pharma.com/en/news-events/asco-2016-phase-i-study-protocol-investigating-iph4102-cutaneous-t-cell-lymphomas [SID:1234513022]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster has been made available on the Company’s website, in the Product Pipeline – IPH4102 section.

About IPH4102 Phase I trial:

The Phase I trial is an open label, multicenter study of IPH4102 in patients with relapsed/refractory CTCL which is performed in Europe (France, Netherlands, United Kingdom) and in the US. Participating institutions include several hospitals with internationally recognized expertise: the Saint-Louis Hospital (Paris, France), the Stanford University Medical Center (Stanford, CA), the Ohio State University (Columbus, OH), the MD Anderson Cancer Center (Houston, Texas), the Leiden University Medical Center (Netherlands), and the Guy’s and St Thomas’ Hospital (United Kingdom). Approximately 60 patients with KIR3DL2-positive CTCL having received at least two prior lines of systemic therapy are expected to be enrolled in two sequential study parts:

A dose-escalation part including approximately 40 CTCL patients in 10 dose levels. Its objective is to identify the Maximum Tolerated Dose and/or the Recommended Phase 2 Dose (RP2D); the dose-escalation follows an accelerated 3+3 design;
A cohort expansion part with 2 cohorts of 10 patients each in 2 CTCL subtypes (transformed mycosis fungoides and Sézary syndrome) receiving IPH4102 at the RP2D until progression. Cohort design (CTCL subtype, number of patients…) may be revisited based on the findings in the dose escalation part of the study.
The primary objective of this trial is to evaluate the safety and tolerability of repeated administrations of single agent IPH4102 in this patient population. The secondary objectives include assessment of the drug’s antitumor activity. A large set of exploratory analyses aims at identifying biomarkers of clinical activity. Clinical endpoints include overall objective response rate, response duration and progression-free survival.

This trial is expected to deliver data for the dose escalation and cohort expansion at the end of 2017 and 2018 respectively.

On June 5, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported positive results from an investigator-sponsored Phase II trial of neratinib with HER2-mutated, non-amplified breast cancer (Press release, Puma Biotechnology, JUN 5, 2016, View Source [SID:1234513015]). The data were presented today in a poster discussion session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in Chicago, Illinois. The poster (Abstract #516), entitled "Phase II Trial of Neratinib for HER2 Mutated, Non-Amplified Metastatic Breast Cancer (HER2 mut MBC)," was presented from 8:00-11:30 a.m. CDT today with a poster presentation discussion occurring immediately following the poster session.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the trial, patients with HER2 mutated breast cancer (either in their primary or metastatic tumor) received 240 mg of neratinib daily. Patients received loperamide (16 mg per day initially) prophylactically for the first cycle of treatment in order to reduce the neratinib-related diarrhea. For the 16 patients enrolled in the trial, 16 patients (100%) had HER2-negative disease, 15 patients (94%) were hormone receptor positive (estrogen receptor or progesterone receptor positive), and for the patients with metastatic disease, patients had received a median of 3 prior regimens (range 2-10 prior regimens) before entering the trial. Among these 16 patients, 14 had activating HER2 mutations and 2 patients had HER2 mutations of unknown significance.

The primary endpoint of the Phase II trial was clinical benefit rate (CBR), defined as complete response (CR), partial response (PR) or stable disease (SD) greater than or equal to 6 months. The trial was designed to detect a CBR of 20%. In the 14 patients with activating HER2 mutations, 5/14 (36%) achieved clinical benefit, including 1 patient (7%) with a CR, 1 patient (7%) with a PR, and 3 patients (21%) with SD for greater than or equal to 6 months. The median duration of response in these 5 patients was 6 (range 6-14+) months. The median progression-free survival for all 14 patients with activating HER2 mutations in the trial was 5.0 months. In the 2 patients with HER2 mutations of unknown significance, there was no clinical benefit seen with neratinib.

Based on the preclinical data that has demonstrated that the combination of an anti-estrogen with a HER2 inhibitor results in enhanced anti-tumor activity in preclinical models of estrogen receptor positive/HER2-mutated breast tumors, the study has been amended to administer the combination of neratinib plus fulvestrant in eligible hormone receptor positive breast cancer patients who have an activating HER2 mutation in the tumor. Enrollment in this cohort is currently ongoing and results from this cohort receiving the combination of fulvestrant plus neratinib will be presented at a future medical meeting.

The interim safety results of the study showed that the most frequently observed adverse event was diarrhea. For the 16 patients enrolled in the study, 4 patients (25%) reported grade 3 diarrhea. The median duration of grade 3 diarrhea for the patients in the study was 1.5 days.

Dr. Cynthia Ma, Associate Professor of Medicine, Clinical Director of the Breast Cancer Program, Section of Medical Oncology, Division of Oncology, at Washington University School of Medicine and principal investigator of the trial, stated, "Neratinib showed promising clinical activity as a single agent in this trial in patients with HER2, non-amplified breast cancer that has an activating HER2 mutation. We look forward to continuing to enroll the cohort that is receiving the combination of neratinib plus fulvestrant and to reporting those results at a future medical meeting."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are very pleased with the preliminary activity seen with neratinib in this cohort of patients with HER2-mutated breast cancer. We look forward to advancing the clinical development of the combination of neratinib and fulvestrant and determining the potential registration path for this combination in 2016."

On June 05, 2016 Oncothyreon Inc. (NASDAQ:ONTY), a clinical-stage biopharmaceutical company, reported the presentation of clinical data on its lead product candidate, ONT-380, at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Oncothyreon, JUN 5, 2016, View Source [SID:1234513013]). ONT-380 is a highly selective small molecule HER2 inhibitor being developed in combination to treat HER2+ advanced or metastatic breast cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Data from a poster presentation (#513 "Efficacy Results of a Phase 1b Study of ONT-380, a CNS-Penetrant TKI, in Combination with T-DM1 in HER2+ Metastatic Breast Cancer (MBC), Including Patients with Brain Metastases") showed promising safety and efficacy results in a Phase 1b study as treatment in patients with progressive disease who were previously treated with trastuzumab and a taxane.

"These results continue to demonstrate the potential of ONT-380 in the treatment of HER2+ breast cancer," said Luke Walker, M.D., Vice President, Clinical Development. "The early evidence of systemic activity, combined with a favorable safety profile and encouraging activity against brain metastases, is supportive of further development of this combination."

"Our internal team and advisors believe that these data are very intriguing and that the T-DM1 combination warrants further exploration," commented Scott Myers, President and CEO. "However, given current resources and the development requirements in this setting, we will pursue this combination in cooperation with others or develop ourselves at a later date. Going forward, we remain focused on advancing our ongoing Phase 2 ‘Triplet’ trial with ONT-380 in combination with capecitabine and trastuzumab."

Updated data from the ongoing "Triplet" Phase 1b trial and the future ONT-380 product development plan will be presented at the Company’s R&D Day on June 14th in New York City.

Summary of Results

The Phase 1b study evaluated ONT-380, an orally bioavailable, highly potent HER2 selective tyrosine kinase inhibitor, in patients with HER2+ metastatic breast cancer previously treated with trastuzumab and a taxane. The study included patients with brain metastases. The data showed:

Activity

Median progression-free survival (PFS) was 8.2 months.
In 34 patients with measurable disease evaluable per RECIST 1.1, an overall response rate of 47% was achieved. Best responses in patients were:
One patient with a complete response and 15 patients with partial responses.
14 (41%) with stable disease, and four patients (12%) with progressive disease.
Safety

The majority of adverse events (AE) were Grade 1.

Most patients requiring a dose reduction of ONT-380 maintained disease control at the lower dose.
Brain metastases

Many of the patients with brain metastases in the study had long-term control of both brain metastases and systemic disease.

Progression-free survival in the 30 patients with brain metastases was similar to patients without brain metastases.

There were no patients without brain metastases at baseline who developed new clinically apparent brain metastases while on the study.