On December 6, 2018 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that results from the subgroup of patients with hormone receptor positive (HR-positive) breast cancer from the Company’s Phase III ExteNET Trial of neratinib for early stage HER2-Amplified breast cancer are being presented at the 2018 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 6, 2018, View Source [SID1234531919]). The presentation entitled, "Efficacy of neratinib in hormone receptor-positive patients who initiated treatment within 1 year of completing trastuzumab-based adjuvant therapy in HER2+ early stage breast cancer: subgroup analyses from the phase III ExteNET trial," is being presented at a poster session by Dr. Frankie Ann Holmes, Texas Oncology/US Oncology Research, Houston Texas on Thursday, December 6 from 7:00 – 9:00 a.m. CST. A copy of this poster is posted on Puma’s website at www.pumabiotechnology.com.

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In September 2018, the European Commission (EC) granted marketing authorisation for NERLYNX (neratinib) for the extended adjuvant treatment of adult patients with early stage hormone receptor positive HER2-overexpressed/amplified breast cancer and who are less than one year from the completion of prior adjuvant trastuzumab based therapy. This poster presentation highlights the data that was the basis for the EC approval.

ExteNET was a Phase III multicenter, randomized, double-blind, placebo-controlled trial of neratinib in adult patients (n=2,840) with early stage HER2-positive breast cancer following adjuvant trastuzumab treatment. Participants were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.

In the subgroup of 1334 patients with hormone receptor positive disease and who were less than one year from the completion of prior adjuvant trastuzumab based therapy, the data, presented in the poster, demonstrated that after two years of follow-up, invasive disease-free survival (iDFS) was 95.3% in the patients treated with neratinib compared with 90.8% in those receiving placebo (hazard ratio = 0.49; 95% CI: (0.30, 0.78); p=0.002). The presentation also showed that after five years of follow-up, invasive disease-free survival (iDFS) was 90.8% in the patients treated with neratinib compared with 85.7% in those receiving placebo (hazard ratio = 0.58; 95% CI: (0.41, 0.82); p=0.002).

The poster highlighted that in this same subgroup, distant disease-free survival (DDFS) was 96.1% in the patients treated with neratinib compared with 92.9% in those receiving placebo (hazard ratio = 0.53, 95% CI: (0.31, 0.88); p=0.015) after two years of follow-up. After five years of follow-up, distant disease-free survival (DDFS) was 92.4% in the patients treated with neratinib compared with 87.7% in those receiving placebo (hazard ratio = 0.57; 95% CI: (0.39, 0.83); p=0.003).

Additionally, in this population, there were 295 patients who did not achieve a pathological complete response (pCR) after treatment with neoadjuvant therapy. This exploratory subgroup is similar to the patient population in the Phase III KATHERINE trial of Kadcyla. The data presented demonstrated that in this subgroup, after two years of follow-up, invasive disease-free survival (iDFS) was 89.9% in the patients treated with neratinib compared with 85.2% in those receiving placebo (hazard ratio = 0.64; 95% CI: (0.30, 1.29)). Longer term follow up demonstrated that at five years, invasive disease-free survival (iDFS) was 85.0% in the patients treated with neratinib compared with 77.6% in those receiving placebo (hazard ratio = 0.60; 95% CI: (0.33, 1.07)).

The profile and frequency of treatment-emergent adverse events in this subgroup of patients with hormone receptor positive disease and who are less than one year from the completion of prior adjuvant trastuzumab was similar compared with the overall safety population. The most common grade 3 treatment-emergent adverse events in this subgroup were diarrhea (neratinib, 39% vs placebo, 1%), nausea (1% vs <1%), and fatigue (2% vs <1%); rates in the overall safety population were diarrhea (neratinib, 40% [included one grade 4 event] vs placebo, 2%), nausea (2% vs <1%), and fatigue (2% vs <1%).

"Reducing the risk of disease recurrence remains a need for patients, despite advances in the treatment of early stage HER2-positive breast cancer," said Professor Michael Gnant, Department of Surgery, Medical University of Vienna, Austria. "This analysis shows that we may be able to provide this type of improvement with neratinib to further reduce this risk of recurrence."

Puma Biotechnology CEO and President Alan H. Auerbach added, "We are encouraged by the data in this patient population and we are committed to continuing to expand NERLYNX accessibility to patients worldwide. We expect NERLYNX to be commercially available in Europe in 2019, beginning with our launch in Germany during the first half of 2019 and followed by additional countries throughout Europe in the second half of 2019."

On December 5, 2018 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that updated data from ongoing Phase I clinical trials of ADCT-402 (loncastuximab tesirine) and ADCT-301 (camidanlumab tesirine) in multiple subtypes of lymphoma during oral and poster presentations at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego (Press release, ADC Therapeutics, DEC 5, 2018, View Source [SID1234596070]).

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"We are encouraged by the safety profiles and strong single-agent anti-tumor activity we continue to observe in the 183-patient first-in-human clinical trial of ADCT-402 and the 113-patient trial of ADCT-301," said Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics. "The updated ADCT-402 data presented at ASH (Free ASH Whitepaper) support its continued evaluation in our ongoing pivotal clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma. For ADCT-301, we now have the dosing data to support further investigation in a planned pivotal Phase II trial in patients with relapsed or refractory Hodgkin lymphoma, which we look forward to initiating in 2019."

ADCT-402 Oral and Poster Presentations at ASH (Free ASH Whitepaper)

Interim Results from the First-in-Human Clinical Trial of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (Abstract 398)

Oral presentation: John Radford, MD, FRCP, Manchester Academic Health Centre, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK

Data were presented from a subpopulation of 139 evaluable patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who had failed or were intolerant to established therapies. The patients had a median age of 63 years and had received a median of three previous therapies. Patients received doses of ADCT-402 ranging from 15 to 200 μg/kg every three weeks. The median number of cycles received was two and the median duration of treatment was 43 days.

Key findings from the oral presentation include:

ADCT-402 has demonstrated manageable toxicity in patients with R/R DLBCL
At doses >120 μg/kg, the overall response rate (ORR) was 43.3% (55/127 patients with DLBCL), comprising 23.6% complete responses and 19.7% partial responses
At doses >120 μg/kg, after a median follow up of 5.5 months, median duration of response (DoR) was not reached in patients achieving a complete response
A pivotal Phase II study is currently enrolling patients with R/R DLBCL to evaluate the efficacy and safety of ADCT-402 at dose 150 μg/kg every three weeks for two cycles followed by dose 75 μg/kg every three weeks (NCT03589469).

Safety and Efficacy of ADCT-402 (Loncastuximab Tesirine), a Novel Antibody Drug Conjugate, in Relapsed/Refractory Follicular Lymphoma and Mantle Cell Lymphoma: Interim Results from the Phase I First-in-Human Study (Abstract 2874)

Poster presentation: Paolo Caimi, MD, Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland, OH

Data were presented from a subgroup of 29 patients, including 14 patients with follicular lymphoma (FL) and 15 patients with mantle cell lymphoma (MCL). The median age of the FL patients was 60.5 years and the median age of the MCL patients was 64 years. Patients received infusions every three weeks at doses ranging from 15 to 200 μg/kg. Patients with FL and MCL received a median of three and two cycles of ADCT-402, respectively.

Key findings from the poster presentation include:

ADCT-402 has demonstrated manageable toxicity in patients with R/R FL and R/R MCL
In patients with FL, ORR was 78.6% (11/14) and median DoR was not reached after a median follow-up time of 11.6 months
In patients with MCL, ORR was 46.7% (7/15) and median DoR was not reached after a median follow-up time of 8.7 months
ADCT-301 Oral and Poster Presentations at ASH (Free ASH Whitepaper)

Phase I Study of ADCT-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate, in Relapsed/Refractory Classical Hodgkin Lymphoma (Abstract 928)

Oral presentation: Mehdi Hamadani, MD, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI

Data were presented from 67 evaluable, heavily pretreated patients with relapsed/refractory (R/R) classical Hodgkin Lymphoma (HL) who had failed or were intolerant to any established therapy known to provide clinical benefit. The median age of the patients was 38 years and they had received a median of five prior therapies. Patients were treated with doses of ADCT-301 ranging from 5 to 300 μg/kg. They completed a median of three cycles of treatment and median treatment duration was 43 days.

Key findings from the oral presentation include:

ADCT-301 has demonstrated manageable toxicity in patients with R/R HL
The most common Grade 3 or 4 treatment-emergent adverse events occurring in at least 5 percent of patients, regardless of attribution, at the 45 μg/kg dose in 37 patients were: maculopapular rash (18.9 percent),elevated gamma-glutamyltransferase (8.1 percent), elevated alanine aminotransferase (8.1 percent), elevated aspartate aminotransferase (2.7 percent), anemia (8.1 percent), Guillain-Barré syndrome / radiculopathy (8.1 percent) and increased lipase (8.1 percent)
In patients with R/R HL, therapy with ADCT-301 achieved an overall response rate (ORR) of 86.5% and a complete response rate of 43% in the 37 patients in the 45 μg/kg dose group who had received and failed prior brentuximab vedotin and most of whom had failed prior checkpoint inhibitor treatment
These data support further investigation of the 45 μg/kg dose of ADCT-301 in a planned pivotal Phase II study anticipated to commence in 2019
ADCT-301 (Camidanlumab Tesirine), a Novel Pyrrolobenzodiazepine-Based CD25-Targeting Antibody Drug Conjugate, in a Phase I Study of Relapsed/Refractory Non-Hodgkin Lymphoma Shows Activity in T-Cell Lymphoma (Abstract 1658)

Poster presentation: Graham P. Collins, MB, BS, DPhil, Oxford University Hospitals, NHS Trust, Oxford, UK

Data were presented from 44 patients with R/R non-Hodgkin lymphoma (NHL) with a median age of 65.5 years who had received a median number of four previous systemic therapies (including prior stem cell transplant). Of those, 22 patients were in a T-cell lymphoma subgroup. Patients were treated with doses of ADCT-301 ranging from 3 to 150 μg/kg and received a median number of two cycles. Median treatment duration was 22 days.

Key findings from the poster presentation include:

ADCT-301 demonstrated an acceptable safety profile during dose-escalation
Overall, in patients with R/R NHL, therapy with ADCT-301 achieved an ORR of 31.7% (13/41) at doses >60 μg/kg
In the R/R T-cell lymphoma subgroup, therapy with ADCT-301 achieved an ORR of 53.8% (7/13) in the 60 and 80 μg/kg dose groups
These data support further investigation of ADCT-301 in T-cell lymphoma
About ADCT-402

ADCT-402 (loncastuximab tesirine) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. ADCT-402 is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (NCT03589469). The U.S. Food and Drug Administration granted orphan drug designation to ADCT-402 for the treatment of DLBCL and mantle cell lymphoma.

About ADCT-301

ADCT-301 (camidanlumab tesirine) is an antibody drug conjugate (ADC) composed of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead. The intra-tumor release of its PBD warhead may cause bystander killing of neighboring tumor cells. In addition, the PBD warhead will trigger immunogenic cell death, which in turn will strengthen the immune response against tumor cells. ADCT-301 is being evaluated in ongoing Phase Ia/Ib clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma (NCT02432235), as well as a Phase Ib clinical trial in solid tumors (NCT03621982).

On December 5, 2018 Apexian Pharmaceuticals reported that Chemotherapy causes chemotherapy-induced peripheral neuropathy (CIPN) in a significant number of patients, yet the pharmaceutical landscape is completely devoid of treatments to prevent CIPN (Press release, Apexian Pharmaceuticals, DEC 5, 2018, View Source [SID1234532133]). The tingling, burning, pain or numbness in the extremities can limit or stop cancer treatment. And, in half the patients affected, CIPN’s symptoms persist five years or more after treatment ends. Apexian Pharmaceuticals aims to change that with their lead compound, APX3330.

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Data presented at the meeting showed continued preclinical support for APX3330 as a potential anti-CIPN treatment, particularly for patients treated with cisplatin or oxaliplatin. Preclinical results presented show APX3330 can block tumor growth while protecting nerve cells.

APX3330, an oral treatment, is currently in a Phase I oncology trial for safety. A Phase II trial is planned in 2019 for anti-tumor and anti-CIPN.

Apexian’s founder and Chief Science Officer, Mark Kelley, PhD, presented the trial’s results in ASCO (Free ASCO Whitepaper)’s Symptom Management Meeting in San Diego, November 16-18, 2018.

Currently ASCO (Free ASCO Whitepaper) does not recommend any drug for preventing or treating CIPN.

"CIPN is a disease with high unmet need and it is exciting to see that APX3330 may have a role to play in addressing the need", says Steve Carchedi, President & CEO of Apexian. "We are committed to developing a portfolio of novel APE1/Ref-1 compound’s that will enhance the lives of patients."

The success of APX3330 builds upon three decades of research by Kelley and his colleagues in modulating a key DNA repair protein, APE1/Ref-1. APX3330 tweaks the protein’s activity to prevent or repair neuronal damage without stimulating cancerous tumors.

APX3330 is Apexian’s lead compound in its growing drug development pipeline.

On December 5, 2018 iCell Gene Therapeutics, LLC reported results from a study ongoing at Chengdu Military General Hospital of ICG144, the first CLL1-CD33 Compound CAR T-cell (cCAR) in clinical study, in patients with particularly difficult to treat Acute Myeloid Leukemia (AML) (Press release, iCell Gene Therapeutics, DEC 5, 2018, View Source [SID1234531930]). Patients 1 and 2 both failed multiple previous cycles of therapy and presented with complex conditions limiting further options. Treatment with CLL1-CD33 cCAR led both patients to complete response and engraftment of haploidentical stem cell transplantation (allo-HSCT) without myeloablative conditioning.

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"Patient response seen to date is encouraging for refractory AML patients, and opens the potential of this novel therapy as bridge to transplant, a supplement to chemotherapy, or as a standalone therapy for patients with acute myeloid leukemia." stated Dr. Fang Liu, MD, PhD, the Principal Investigator of the study who presented the results at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego. Dr. Yupo Ma, MD, PhD, Chairman of iCell Gene Therapeutics added, "Initial patient experience highlights the potential importance of iCell’s proprietary multiple antigen targeting and enhancing technologies to overcome antigen escape and improve treatment outcomes."

Upon enrollment, patients receive a lymphodepletion regimen consisting of fludarabine and cyclophasphamide followed by 1×106 – 2×106 CAR T cells/kg, nonmyeloablative conditioning and Haplo-HSCT

Patient 1 is a 6-year-old originally diagnosed with Franconi anemia transformed JMML and eventually to AML-M5 with more than 90% blasts in the marrow, complex karyotype and FLT3-ITD mutation.
Patient 2 is a 23-year-old, failed to TKIs, AP-CML (basophils>20%, plt>1000X109/L), T315I mutation.
Complete response and Haplo-HSCT engraftment was observed in both patients.
Grade 1 CRS and pancytopenia was observed in both patients.
Grade 3 neurotoxicity was observed in Patient 1.
About CLL1-CD33 cCAR T cell therapy

CLL1-CD33 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressed on a T-cell, directed against the surface proteins CLL1 and CD33. The diseases treated by CLL1-CD33 cCAR could include acute myeloid leukemia, myelodysplastic syndromes, chronic myeloid leukemia and chronic myeloproliferative neoplasms. CLL1 is associated with leukemia stem cells and disease relapse, while CD33 is expressed on bulky AML disease. Treatment of AML is a challenge due to heterogeneity of AML bearing cells, which renders single antigen targeting CAR T-cell therapy ineffective. ICG144 cCAR is designed to target the mechanisms of single-CAR relapse, specifically antigen escape and leukemic stem cells.

About AML

Acute myeloid leukemia (AML) is the abnormal proliferation of immature myeloid cells and the most common leukemia in adults. Prognosis is dismal when AML relapses or is refractory to chemotherapy. Mortality associated with this disease is high, with approximately 10,000 deaths in 2018 in the US.

On December 5, 2018 Protagonist Therapeutics, Inc. (NASDAQ:PTGX) reported that Dinesh V. Patel, Ph.D., President and Chief Executive Officer, will provide a corporate overview at the BMO Capital Markets 2018 Prescriptions for Success Healthcare Conference in New York (Press release, Protagonist, DEC 5, 2018, View Source;p=RssLanding&cat=news&id=2379597 [SID1234531922]).

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Presentation details:

Event:

BMO Capital Markets 2018 Prescriptions for Success Healthcare Conference

Date:

Wednesday, Dec. 12, 2018

Time:

9:20 a.m. EST

A live and archived audio webcast of the presentation can be accessed by visiting the Investors page of the Protagonist Therapeutics website at View Source