On October 22, 2018 CytomX Therapeutics, Inc. (Nasdaq:CTMX) a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, today presented clinical results from two arms of the PROCLAIM (PRObody CLinical Assessment In Man) module, PROCLAIM-072 (Press release, CytomX Therapeutics, OCT 22, 2018, View Source [SID1234530036]). PROCLAIM-072 is an ongoing Phase 1/2 trial evaluating CX-072, a Probody therapeutic targeting PD-L1, as monotherapy and in combination with Yervoy (ipilimumab) or Zelboraf (vemurafenib) in patients with advanced, unresectable solid tumors. Data from the CX-072 monotherapy arm and ipilimumab combination arm were presented today in two posters at the 2018 Annual Meeting of the European Society of Clinical Oncology (ESMO) (Free ESMO Whitepaper) in Munich, Germany. The data presented at ESMO (Free ESMO Whitepaper) were based on an August 3, 2018 data cutoff, reflecting an approximately three-month difference from the data cutoff for the presentations made at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June.

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"Our data presented today continue to support our thesis that CX-072 has potential to be a new and differentiated combination partner for anti-cancer therapy. CX-072 has demonstrated activity both as monotherapy and in combination with ipilimumab and is generally well tolerated in both regimens," said Sean McCarthy D.Phil., president and chief executive officer of CytomX Therapeutics. "We are advancing monotherapy CX-072 towards registrational studies and continuing to explore the full potential of the CX-072/ipilimumab combination. With the clinical data reported today, and at ASCO (Free ASCO Whitepaper), the Probody platform is declaring its potential to deliver multiple opportunities to make a meaningful difference for cancer patients."

Poster 435 – Preliminary Results of PROCLAIM-072: The First-In-Human, Dose-Finding Trial of PD-L1 Probody Therapeutic CX-072 as Monotherapy in Patients with Advanced Solid Tumors

Presenter: Valentina Boni, M.D., Ph.D., Clinical Researcher, START Madrid and Associate Professor, University CEU San Pablo in Madrid, Spain

The primary objectives of Parts A and A2 of this first-in-human, dose-escalation, monotherapy arm are to assess safety and tolerability, including determination of the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of CX-072 as monotherapy. Patients in Part A received escalating doses of CX-072 from 0.03 mg/kg to 30 mg/kg. Patients in Part A2 received escalating doses of CX-072 from 0.3 mg/kg to 10 mg/kg and had mandatory biopsies of PD-L1 positive solid tumors. At the time of the August 3, 2018 data cutoff, Parts A and A2 had enrolled 46 patients, with 11 patients still receiving treatment. Treatment duration for patients in Part A2 was limited at higher doses. Enrollment in Part A is complete and Part A2 is ongoing with patient follow-up ongoing.

Monotherapy Well Tolerated

The maximum tolerated dose (MTD) was not reached. As of an August 3, 2018 data cutoff, results were consistent with previous analyses. The administration of monotherapy CX-072 was generally well tolerated with the majority of treatment-related adverse events (TRAEs) Grade 1/2. Of the 46 treated patients, 5 (11%) reported Grade 3/4 TRAEs and 3 (7%) reported treatment-related serious adverse events (SAEs). Immune-related adverse events (irAE) were reported in 3 (7%) of patients.

Monotherapy Clinical Activity

As of an August 3, 2018 data cutoff, results showed that among 38 evaluable patients who received CX-072, objective responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were observed in 3 (8%) patients, all treated at a dose of > 3 mg/kg: PD-L1 negative triple negative breast cancer (confirmed partial response (cPR); 10 mg/kg), thymic cancer (unconfirmed partial response (uPR); 3 mg/kg), and cervical cancer (uPR; 10 mg/kg). Stable disease was observed in 15 (39%) of patients for an overall disease control rate of 47%. For the 18 patients who received CX-072 ≥3 mg/kg, objective responses were observed in 3/18 (17%) and the disease control rate was 61%. Decreased target lesions were observed in 38% (14/37) of all evaluable patients with measurable disease at baseline and in 59% (10/17) of the subset of patients who received > 3 mg/kg of CX-072.

Poster 436 – Preliminary Interim Results of the First-In-Human, Dose-Finding PROCLAIM-072 Trial Evaluating the PD-L1 Probody Therapeutic CX-072 in Combination with Ipilimumab in Patients with Advanced Solid Tumors

Presenter: Ruth Plummer, M.D., Northern Institute for Cancer Research, Newcastle University

The primary objectives of this ongoing arm of the study are to assess safety and tolerability, and to determine the MTD and DLT of CX-072 when administered in a concomitant combination schedule with ipilimumab. At the August 3, 2018 data cutoff, the study had enrolled 20 immunotherapy naïve patients who had received an average of 3 prior anti-cancer treatments in a variety of tumor types for which no anti-PD-1 or PD-L1 agents were available for their disease. Patients received the combination ipilimumab (3 mg/kg or greater) and CX-072 (escalating doses of 0.3 mg/kg to 10 mg/kg) every three weeks for four cycles followed by monotherapy CX-072 every two weeks.

Combination with Ipilimumab Well Tolerated

As of the August 3, 2018 data cutoff date, the MTD had not yet been reached and was generally well tolerated with no new safety signals observed beyond those expected for each component of the CX-072 plus ipilimumab combination. The full dose of 3 mg/kg of ipilimumab in combination with CX-072 10 mg/kg was well tolerated. The majority of TRAEs were Grade 1/2. Of the 20 treated patients, 4 (20%) reported a Grade 3/4 TRAE, a rate similar to that reported previously for 3 mg/kg ipilimumab monotherapy1. These events included: Grade 3 colitis (n=1), Grade 3 dyspnea/Grade 3 pneumonitis (n=1), Grade 3 headache/Grade 3 hyponatremia (n=1), and Grade 3 amylase/Grade 4 lipase (n=1). Grade 3/4 irAEs were reported in 2/20 (10%) patients, 0% (0/11) at doses of >3 mg/kg CX-072 with 3 mg/kg of ipilimumab. The study is still ongoing with enrollment and dose escalation continuing.

1 Larkin J, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373: 23–34.

Ipilimumab Combination Clinical Activity

As of an August 3, 2018 data cutoff, results also showed that among 14 evaluable patients who received ipilimumab (3 mg/kg) combined with CX-072 (0.3 to 10 mg/kg), 3 (21%) achieved objective responses by RECIST v1.1, including patients with: anal cancer (confirmed complete response (cCR); 0.3 mg/kg CX-072), testicular cancer (confirmed partial response (cPR); 1 mg/kg CX-072) and cancer of unknown primary (cPR; 3 mg/kg CX-072). Stable disease was observed in 3 additional patients for a disease control rate of 43%. As of the data cutoff, all 3 of the responders remained on treatment with durations of response of 7.4, 5.3, and 3.2 months, respectively.

Probody Pharmacokinetics

Results from a preliminary single-dose pharmacokinetic analysis of single-agent CX-072 suggest that, as designed, CX-072 circulates predominantly as the intact masked prodrug across all dose levels with 96% intact at 30 mg/kg. Further, CX-072 is only minimally influenced by target mediated drug disposition at low doses, suggesting that masking is effective in blocking interaction with PD-L1 in the periphery.

CX-072 Monotherapy and Ipilimumab Combination Expansion Arms

Based upon the results from the Part A CX-072 monotherapy arm presented at ASCO (Free ASCO Whitepaper) in June, in the second quarter, the Company began dosing patients in Part D, the expansion arm examining CX-072 as monotherapy at 10 mg/kg in 8 undisclosed tumor types. The Company has the potential to move one or more of these indications into a registrational trial with the goal of advancing towards commercialization. The Company expects initial Part D clinical data in 2019.

The Company is currently dosing patients in the Part B CX-072 combination with ipilimumab arm at 6 mg/kg of ipilimumab. The Company plans to initiate expansion modules with this combination in the first half of 2019 at doses and indications to be determined.

Conference Call and Webcast

CytomX will host a conference call and live webcast with slides today, Monday, October 22, 2018, beginning at 2:30 p.m. CEST/ 8:30 a.m. EDT to discuss these data presentations and review the next steps for the programs. This event can be accessed in three ways:

From the CytomX website: View Source Please access the website 15 minutes prior to the start of the call to download and install any necessary audio software.

By telephone: Participants can access the call by dialing 1-877-809-6037 (United States) or 1- 615-247-0221 (International) referencing Conference ID 1275596.

By replay: A replay of the webcast will be located under the Investor Relations section of CytomX’s website approximately two hours after the conclusion of the live call and will be available for 30 days following the call.
About PROCLAIM

PROCLAIM (Probody Clinical Assessment In Man) is an international umbrella program designed to evaluate CytomX’s Probody therapeutics. The first module is the PROCLAIM-CX-072 clinical program, an open-label, dose-finding Phase 1/2 trial evaluating CX-072 as monotherapy and in combination with Yervoy (ipilimumab) or Zelboraf (vemurafenib) in patients with metastatic or locally advanced unresectable solid tumors or lymphomas. CytomX aims to achieve three goals as part of the PROCLAIM-072 clinical trial:

Tolerability: Demonstrate that CX-072 is well tolerated in patients and potentially improves safety, particularly in the combination setting.
Anti-cancer activity: Demonstrate initial evidence of CX-072’s anti-cancer activity as monotherapy and in combination.
Translational program and Probody platform proof-of-concept: Explore mechanistic aspects of Probody activity in patients as observed in preclinical models.

On October 22, 2018 SELLAS Life Sciences Group, Inc. (Nasdaq:SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported data from the prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial of the combination of nelipepimut-S (NeuVax, NPS) +/- trastuzumab (Herceptin) targeting HER2 low-expressing breast cancer patient cohorts (Press release, Sellas Life Sciences, OCT 22, 2018, View Source [SID1234530035]). The data were presented in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Meeting, being held in Munich, Germany.

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"These data presented at ESMO (Free ESMO Whitepaper) today highlight the therapeutic potential of NPS for patients with early-stage triple negative breast cancer (TNBC), who currently face limited and ineffective treatment options in the adjuvant setting," said Dr. Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The combination of NPS and trastuzumab demonstrated a clinically meaningful and statistically significant difference in the cohort of patients with TNBC with a 75.2% reduction in risk of relapse or death at 26 months. Importantly, following review of the final data that were also assessed by the independent Data Safety Monitoring Board (DSMB) on October 15, 2018, there was an incremental further improvement of clinical benefit to patients now observed in comparison with the data from the interim analysis completed more than six months ago."

The key data from today’s presentation, based on the final analysis, are shown below, including the summary table and the Kaplan-Meier (K-M) survival curve showing specifically the TNBC cohort:

Safety: Most treatment-emergent adverse events (TEAEs) were of mild or moderate (G1/2) severity (local: 98%; systemic: 93%). The majority of G3 systemic TEAEs were unrelated to NPS. Treatment-related adverse events consisted of manageable local injection site reactions, skin induration, pruritus, and fatigue.

Efficacy:
Outcomes Summary (comparison between the 2-arms of the study, i.e., Active: NPS + TZ, and Control: TZ alone):

Notably, the patient demographics and baseline disease characteristics were well balanced between the two arms, both in the intention-to-treat (ITT) and TNBC populations.

Elizabeth A. Mittendorf, M.D., Ph.D., Rob and Karen Hale Distinguished Chair in Surgical Oncology, Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital, Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center, and the Principal Investigator of the Phase 2b study commented: "It is encouraging to see that the final analysis of the NPS +/- trastuzumab Phase 2b trial for the TNBC cohort not only confirms the previously reported positive data, presented in full today, but also provides evidence for a significant clinically positive outcome with the combination. In many early stage TNBC patients, the benefit of initial treatment with neoadjuvant chemotherapy is incomplete, leaving room for improvement, especially in the adjuvant or maintenance setting. To date, targeted therapies have not proven effective for TNBC. Putting HER2 in the crosshairs of an immunotherapeutic combination, in this case NPS plus trastuzumab in triple-negative (HER2 IHC 1+/2+; hormone receptor negative) breast cancer patients, makes sense biologically considering preexisting activated cellular immunity in most patients with these tumors and the pharmacodynamic synergy between these two agents."

Dr. Stergiou further stated, "We look forward to continuing our discussions with U.S. and European regulatory agencies on the most optimal and expeditious development path for NPS in TNBC. To that end, we will be meeting with the FDA in December. We are also engaging in ongoing discussions with potential partners. I would like to thank all patients who participated in this NPS study, and their families and outstanding physicians, as well as our team at SELLAS and our supportive stockholders. As October is breast cancer awareness month, one could not have thought of a better timing to present this data, consistent with our mission to develop potentially life-saving drugs for patients in need."

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

Conference Call

SELLAS will host a conference call on Monday, October 22, 2018 at 8:00 a.m. ET to discuss these data. To participate in the conference call, please dial (866) 416-7995 (domestic) or +1 (409) 217-8225 (international) and refer to conference ID 5571389. A live webcast of the call can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.sellaslifesciences.com.

An archived webcast recording will be available on the SELLAS website beginning approximately two hours after the call.

About ESMO (Free ESMO Whitepaper)

The European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) is Europe’s leading non-profit medical oncology organization. ESMO (Free ESMO Whitepaper) is a membership-based society, comprising of 500 expert committee members and 18,000 oncology professionals. ESMO (Free ESMO Whitepaper) organizes a large number of meetings to provide its members and the community with the resources they need and also plays a major role in public policy and European affairs. The ESMO (Free ESMO Whitepaper) 2018 Annual Meeting represents a multi-professional platform for oncology education and exchange, and for immense international visibility for scientific research, and will be held under the tagline "Securing access to optimal cancer care."

On October 22, 2018 GTx, Inc. (Nasdaq: GTXI) reported financial results for the third quarter ended September 30, 2018, and provided a corporate update (Press release, GTx, OCT 22, 2018, View Source [SID1234530034]).

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"During the quarter, we turned our focus to the ongoing selective androgen receptor degrader program and the potential of our novel selective androgen receptor degrader to treat castration-resistant prostate cancer. We expect to select the most appropriate development compounds by year-end, which we plan to take into IND-enabling studies next year," said Robert J. Wills, Ph.D., Executive Chairman of GTx. "Additionally, we are exploring other strategic options for the company with the goal of optimizing the full potential of our development pipeline."

Corporate Development Update

Selective Androgen Receptor Degrader (SARD): Prostate Cancer

The Company has an ongoing preclinical program to evaluate its novel selective androgen receptor degrader (SARD) technology in castration-resistant prostate cancer (CRPC). In some men with CRPC, current prostate cancer therapy is not effective or subject to emerging resistance. The Company believes that its SARDs may be first-in-class dual-interacting androgen receptor (AR) antagonists and degraders, and may therefore potentially treat CRPC in men who are non-responsive to current androgen targeted therapies. Going forward, the Company plans to:

Complete ongoing mechanistic preclinical studies by year-end or early in the first quarter of 2019;
Select the most appropriate SARD compounds to move forward with IND-enabling studies in 2019; and
Potentially advance one of its SARD compounds into a first-in-human clinical trial in 2020
Selective Androgen Receptor Modulator (SARM): Stress Urinary Incontinence (SUI), Breast Cancer

SUI: Enobosarm, a SARM, was evaluated in post-menopausal women with SUI compared to placebo. During the quarter, the Company announced that the ASTRID Trial, a Phase 2 double-blind, placebo-controlled clinical trial of orally-administered enobosarm (3 mg or 1 mg) in post-menopausal women with SUI, did not achieve statistical significance on the primary endpoint for the trial. Enobosarm was generally safe and well tolerated, and reported adverse events were minimal and similar across all treatment groups. The Company is conducting a comprehensive review of all the ASTRID data and is consulting with key experts to fully understand the study outcomes.

Advanced Breast Cancer: Enobosarm was also evaluated as a hormonal therapy for women with estrogen receptor positive (ER+) and androgen receptor positive (AR+) breast cancer in a Phase 2 clinical trial. The trial met the primary efficacy endpoint in the trial; there are three women in the study who continue to respond to treatment after almost two years on enobosarm (two have stable disease, one now has a partial response). Approximately one year ago, the Company determined that treatment paradigms had shifted to immunotherapies and/or combination therapies, and that it was no longer feasible for GTx to conduct further development of enobosarm in breast cancer.

Enobosarm has been evaluated in more than two dozen clinical trials enrolling over 2,200 subjects, in which approximately 1,500 subjects were treated with enobosarm at doses ranging from 0.1 mg to 100 mg. At all evaluated dose levels, enobosarm was observed to be generally safe and well tolerated.

Third Quarter 2018 Financial Results

As of September 30, 2018, cash and short-term investments were $38.1 million compared to $43.9 million at December 31, 2017.
Research and development expenses for the quarter ended September 30, 2018 were $7.5 million compared to $5.9 million for the same period of 2017.
General and administrative expenses for the quarter ended September 30, 2018 were $2.2 million compared to $2.6 million for the same period of 2017.
The net loss for the quarter ended September 30, 2018 was $9.4 million compared to a net loss of $8.5 million for the same period in 2017.
Net loss for the nine months ended September 30, 2018 was $33.0 million compared to a net loss of $21.2 million for the same period in 2017.
GTx had approximately 24.1 million shares of common stock outstanding as of September 30, 2018. Additionally, there are warrants outstanding to purchase approximately 5.3 million shares of GTx common stock at an exercise price of $8.50 per share and approximately 3.3 million shares of GTx common stock at an exercise price of $9.02.

On October 22, 2018 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that preliminary clinical data from an ongoing Phase 1 trial of its investigational PARP inhibitor, pamiparib, in combination with low-dose temozolomide in patients with locally advanced or metastatic solid tumors were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, being held in Munich, Germany (Press release, BeiGene, OCT 22, 2018, View Source;p=irol-newsArticle&ID=2372634 [SID1234530033]). Discovered by BeiGene scientists in Beijing, pamiparib is currently in Phase 3 trials globally and in China as a monotherapy and in Phase 1/2 trials in combination with chemotherapy or immunotherapy for a variety of solid tumors.

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"In prior non-clinical studies, pamiparib has been shown to not only inhibit PARP from repairing damaged DNA, but also trap PARP on DNA undergoing repair, which we believe furthers its potential for anti-tumor activity. This study evaluates the combination of low-dose temozolomide, a DNA damaging agent, with full-dose pamiparib to assess the potential for PARP trapping, and is part of our effort to advance the global development of pamiparib as both a monotherapy and in combination," commented Amy Peterson, M.D., Chief Medical Officer for Immuno-Oncology of BeiGene.

"Preliminary results demonstrate antitumor activity across a variety of indications and regardless of known BRCA mutation status. That, combined with the preliminary safety and tolerability profile, support the continued development of this combination," said Melissa Johnson, M.D., Associate Director, Lung Cancer Research Program, Sarah Cannon Research Institute and lead author of the poster presentation.

Summary of Preliminary Results

This open-label, multi-center Phase 1b dose-escalation trial of pamiparib plus low- dose temozolomide (TMZ) (NCT03150810) was designed to evaluate the safety, tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity of the combination in patients with locally advanced and metastatic tumors. Patients received full-dose pamiparib (60mg twice a day) in combination with escalating doses of TMZ, administered in both pulse and continuous dosing schedules.

As of August 24, 2018, a total of 40 patients with solid tumors have been enrolled in the study. The most frequent tumor types were prostate cancer (n=7), small cell lung cancer (n=6), breast cancer (n=4), epithelial ovarian cancer (n=4), and pancreatic cancer (n=3). Patients had received a median of four prior lines of therapy (1-10). The median duration of treatment was 1.6 months (0-9). As of the data cutoff, a total of 18 patients (45%) remained on pamiparib and TMZ treatment.

The combination was shown to be generally well tolerated. Dose-limiting grade 4 neutropenia was observed in two patients treated with 120 mg TMZ Days 1-7 and two patients treated with 100 mg TMZ Days 1-7. The most common treatment-emergent adverse events (TEAEs), regardless of grade or attribution, were nausea (52.5%), anemia (37.5%), neutropenia (30%), thrombocytopenia (27.5%), and fatigue (27.5%). TEAEs grade ≥3 occurred in 18 patients. The most common grade 3 or 4 adverse events (AEs) were neutropenia (27.5%), anemia (22.5%), and thrombocytopenia (20%). Cytopenias were manageable and reversible. Two patients experienced AEs that resulted in discontinuation of pamiparib and TMZ, one of which was considered related to study treatment. Serious AEs considered related to study treatment occurred in four patients (neutropenia, abdominal abscess, thrombocytopenia and leukopenia, and dehydration). There were no AEs with fatal outcome.

Twenty-three patients with solid tumors other than prostate cancer were evaluable per RECIST v1.1 (defined as having at least one post-baseline tumor assessment or at least nine weeks of follow-up). Preliminary data showed that two patients achieved a confirmed partial response (PR), including one patient with pancreatic cancer (treated with 40 mg TMZ Days 1-28), and one patient with small cell lung cancer (80 mg TMZ Days 1-7). Two additional patients achieved an unconfirmed PR, including one patient with BRCA-mutated triple-negative breast cancer treated with 80 mg TMZ Days 1-7, and one patient with urothelial cancer treated with 40mg TMZ Days 1-7. Ten patients had a best response of stable disease (SD); four patients had a best response of disease progression; and five patients were not evaluable for RECIST response either due to lack of a post-baseline tumor assessment or non-measurable disease at baseline.

All seven patients with prostate cancer were evaluated per the Prostate Cancer Working Group 2 (PCWG2) criteria. Of these, one patient (confirmed BRCA wildtype) achieved a visceral PR and prostate-specific antigen (PSA) response at the first post-baseline tumor assessment, and one patient achieved SD, who remains on study for over 270 days.

About Pamiparib
Pamiparib (BGB-290) is an investigational inhibitor of PARP1 and PARP2 which has demonstrated pharmacological properties such as brain penetration and PARP-DNA complex trapping in preclinical models. Discovered by BeiGene scientists in Beijing, pamiparib is currently in global clinical development as a monotherapy and in combination with other agents for a variety of solid tumor malignancies.

On October 22, 2018 Celgene Corporation (NASDAQ:CELG) reported the first results from the IMpassion130 study evaluating ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in combination with atezolizumab (Tecentriq) in patients with first-line locally advanced triple negative breast cancer (TNBC) and the IMpower130 study evaluating ABRAXANE/carboplatin in combination with atezolizumab in first-line advanced non-squamous non-small cell lung cancer (Press release, Celgene, OCT 22, 2018, View Source [SID1234530032]). These findings were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress, taking place from October 19-23 in Munich, Germany. Both studies were sponsored by Roche.

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IMpassion130 Demonstrated a PFS Benefit of ABRAXANE plus Atezolizumab Combination as Initial Treatment in Locally Advanced or Metastatic TNBC

Results from the Phase 3 Impassion study showed that the investigational combination of ABRAXANE plus atezolizumab significantly reduced the risk of disease worsening or death (PFS) in first-line metastatic or unresectable locally advanced TNBC patients compared to ABRAXANE alone (7.2 months vs. 5.5 months [p=0.0025; HR=0.80 (95% CI: 0.69,0.92)]) in all randomized patients and in the PD-L1 positive subgroup population (median PFS=7.5 months vs. 5.0 months; HR=0.62(95% CI: 0.49-0.78, p<0.0001).

At this first interim analysis, statistical significance was not met for overall survival (OS) in the ITT population (median OS=21.3 months in the ABRAXANE plus atezolizumab arm vs. 17.6 months in the ABRAXANE monotherapy arm; HR=0.84, 95% CI 0.69-1.02, p=0.0840). In the PD-L1-positive population (which was not tested due to hierarchal design), the ABRAXANE plus atezolizumab arm demonstrated a 9.5-month OS improvement (median OS=25.0 vs. 15.5 months; HR=0.62, 95% CI 0.45-0.86). Follow-up will continue until the next planned analysis. The safety findings were consistent with the known profiles of the individual regimens investigated.

IMpassion130 is the first phase III study to demonstrate a statistically significant PFS improvement in first-line metastatic or unresectable locally advanced TNBC.

"The findings of the IMpassion130 trial illustrate that the ABRAXANE plus atezolizumab regimen has activity in an aggressive type of breast cancer with few viable treatments," said Jay Backstrom, M.D., Chief Medical Officer and Head of Global Regulatory Affairs for Celgene. "We are particularly excited about these findings because triple negative breast cancer is such a difficult disease to treat and patients are in need of additional treatment options."

The most common Grade 3/4 treatment-emergent adverse events (TEAE) were neutropenia (8% in both treatment arms), decreased neutrophil count (ABRAXANE plus atezolizumab: 5%; ABRAXANE plus placebo: 3%), peripheral neuropathy (ABRAXANE plus atezolizumab: 6%; ABRAXANE plus placebo: 3%), fatigue (ABRAXANE plus atezolizumab: 4%; ABRAXANE plus placebo: 3%) and anemia (3% in both treatment groups). A higher proportion of patients in the ABRAXANE plus atezolizumab arm reported serious AEs (23% vs. 18%).

IMpower130 Demonstrated Significant OS and PFS Benefit of ABRAXANE/Carboplatin plus Atezolizumab in Advanced Non-Squamous NSCLC

Results from the Phase III IMpower130 study showed that first-line treatment with the investigational combination of ABRAXANE/carboplatin plus atezolizumab significantly improved overall survival of patients with previously untreated metastatic non-squamous NSCLC compared to ABRAXANE/carboplatin alone (median OS= 18.6 versus 13.9 months; HR= 0.79; 95 percent CI: 0.64–0.98; p=0.033) in the intention-to-treat wild-type (ITT-WT) population. The ABRAXANE/carboplatin plus atezolizumab combination also significantly reduced the risk of disease worsening or death (PFS) compared to ABRAXANE/carboplatin alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95 percent CI: 0.54–0.77; p<0.0001) in the ITT-WT population.

Safety for the ABRAXANE/carboplatin plus atezolizumab combination appeared consistent with the known safety profile of the individual medicines. Grade 3/4 TEAEs were reported in 73.2 percent of people receiving ABRAXANE/carboplatin plus atezolizumab compared to 60.3 percent of people receiving ABRAXANE/carboplatin alone. The most common Grade 3/4 AEs in people receiving ABRAXANE/carboplatin plus atezolizumab were: an abnormal low count of a certain type of white blood cell (neutropenia, 32.1 percent), a decrease in red blood cells (anemia, 29.2 percent) and a decreased neutrophil count (12.1 percent).

"Data from these studies continue to shape our understanding of the current and future treatment landscapes in areas where historically there have been limited treatment options available to patients," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "We are very encouraged by the findings of these studies as they add to the growing body of research evaluating the potential of ABRAXANE as a backbone therapy in combination with immunotherapy."

ABRAXANE alone or in combination with atezolizumab is not approved for the first-line treatment of triple negative breast cancer, and ABRAXANE/carboplatin in combination with atezolizumab is not approved for the treatment of advanced NSCLC.

Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About the IMpassion130 study

IMpassion130is a Phase III multicenter, randomized, double-blind study evaluating the efficacy, safety, and pharmacokinetics of ABRAXANE and atezolizumabcompared with placebo in combination with ABRAXANE alone in patients with locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer (mBC). The study enrolled 902 people who were randomized equally (1:1). The co-primary endpoints were PFS (RECIST 1.1) in all randomized participants, as well as in those who disease expressed PD-L1, and OS in all randomized participants. Secondary endpoints included overall response rate, duration of response and time to deterioration in Global Health Status/Health-Related Quality of Life.

During the treatment duration, people in:

Arm Areceived atezolizumab at a fixed dose of 840 milligrams via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle and ABRAXANE at a dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle.ABRAXANEwas administered for a target of at least 6 cycles, with no maximum. Participants received both agents until unacceptable toxicity or disease progression.
Arm Breceived ABRAXANE at a dose of 100 milligrams per square meter via IV infusion on Days 1, 8, and 15 of each 28-day cycle. ABRAXANE was administered for a target of at least 6 cycles, with no maximum, and placebo was administered via IV infusion on Days 1 and 15 of each 28-day cycle. Participants assigned to placebo plus ABRAXANE received both agents until unacceptable toxicity or disease progression.
About the IMpower130 study

IMpower130 is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of atezolizumab in combination with carboplatin and ABRAXANE versus chemotherapy (carboplatin and ABRAXANE) alone for chemotherapy-naïve patients with stage IV non-squamous NSCLC. The study enrolled 723 people who were randomized (2:1) to receive:

Atezolizumab (1200 mg via IV every 3 weeks) plus carboplatin (AUC 6 mg/mL/min via IV every 3 weeks) and ABRAXANE (100 mg/m2 via IV every 3 weeks) (Arm A), or
Carboplatin (AUC 6 mg/mL/min via IV every 3 weeks) and ABRAXANE (100 mg/m2 via IV every 3 weeks) (Arm B, control arm)
During the treatment-induction phase, people in Arm A received atezolizumab and carboplatin on day 1 of each 21-day cycle, and ABRAXANE on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurs first. People received atezolizumab during the maintenance treatment phase until loss of clinical benefit was observed.

During the treatment-induction phase, people in Arm B received carboplatin on day 1 and ABRAXANE on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurred first. People received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover to receive atezolizumab as monotherapy until disease progression.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the ITT-WT population
OS in the ITT-WT population
About ABRAXANE

ABRAXANE is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non–small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm 3 . In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of <1500 cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC) and 47% of patients with non–small cell lung cancer (NSCLC)
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1 (for MBC) and Days 1, 8, and 15 for NSCLC
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3
In the case of severe neutropenia (<500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with either MBC or NSCLC
In patients with MBC, resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level >1500 cells/mm3 and platelets recover to a level >100,000 cells/mm3
In patients with NSCLC, resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle
Nervous System

Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to Grade 1 or 2 for MBC or until resolution to ≤ Grade 1 for NSCLC followed by a dose reduction for all subsequent courses of ABRAXANE
Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Cross-hypersensitivity between ABRAXANE and other taxane products has been reported and may include severe reactions such as anaphylaxis. Patients with a previous history of hypersensitivity to other taxanes should be closely monitored during initiation of ABRAXANE therapy
Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
For MBC and NSCLC, the starting dose should be reduced for patients with moderate or severe hepatic impairment
Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood
Embryo Fetal Toxicity

Based on mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman
Advise females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with ABRAXANE and for at least six months after the last dose of ABRAXANE
Advise male patients with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE
ADVERSE REACTIONS

Randomized Metastatic Breast Cancer (MBC) Study

The most common adverse reactions (≥20%) with single-agent use of ABRAXANE vs paclitaxel injection in the MBC study are alopecia (90%, 94%), neutropenia (all cases 80%, 82%; severe 9%, 22%), sensory neuropathy (any symptoms 71%, 56%; severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe 8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%, 31%), anemia (any 33%, 25%; severe 1%, <1%), nausea (any 30%, 22%; severe 3%, <1%), diarrhea (any 27%, 15%; severe <1%, 1%) and infections (24%, 20%), respectively
Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients
Other adverse reactions of note with the use of ABRAXANE vs paclitaxel injection included vomiting (any 18%, 10%; severe 4%, 1%), fluid retention (any 10%, 8%; severe 0%, <1%), mucositis (any 7%, 6%; severe <1%, 0%), hepatic dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%, 3%; severe <1%, <1%), neutropenic sepsis (<1%, <1%), and injection site reactions (<1%, 1%), respectively. Dehydration and pyrexia were also reported
Renal dysfunction (any 11%, severe 1%) was reported in patients treated with ABRAXANE (n=229)
In all ABRAXANE-treated patients (n=366), ocular/visual disturbances were reported (any 13%; severe 1%)
Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients and included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension
Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported
Non–Small Cell Lung Cancer (NSCLC) Study

The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue
The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%)
The following common (≥10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin–treated and paclitaxel injection plus carboplatin–treated patients: alopecia (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash (10%); incidence rates are for the ABRAXANE plus carboplatin treatment group
Adverse reactions with a difference of ≥2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%), respectively
Adverse reactions with a difference of ≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%, 19%), respectively
Neutropenia (all grades) was reported in 85% of patients who received ABRAXANE and carboplatin vs 83% of patients who received paclitaxel injection and carboplatin
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied. In postmarketing experience, cross-hypersensitivity between ABRAXANE and other taxanes has been reported
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS

Pregnancy

Based on the mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman. Advise females of the potential risk to a fetus and to avoid becoming pregnant while receiving ABRAXANE
Lactation

Paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Nursing must be discontinued when receiving treatment with ABRAXANE and for two weeks after the last dose
Females and Males of Reproductive Potential

Females of reproductive potential should have a pregnancy test prior to starting treatment with ABRAXANE
Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with and for at least six months after the last dose of ABRAXANE [see Warnings and Precautions]
Advise males with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE [see Warnings and Precautions]
Based on findings in animals, ABRAXANE may impair fertility in females and males of reproductive potential
Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric

A higher incidence of epistaxis, diarrhea, dehydration, fatigue, and peripheral edema was found in patients 65 years or older who received ABRAXANE for MBC in a pooled analysis of clinical studies
Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC
Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min)
DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
For MBC and NSCLC, reduce starting dose in patients with moderate to severe hepatic impairment
Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicity
Monitor patients closely