On June 4, 2018 Pfizer Inc. (NYSE:PFE) reported overall survival (OS) data from the ARCHER 1050 trial evaluating dacomitinib as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations compared to gefitinib (Press release, Pfizer, JUN 4, 2018, View Source [SID1234527151]). The trial showed a median OS of 34.1 months for patients receiving dacomitinib (95% CI: 29.5, 37.7), representing a more than seven-month improvement compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). The OS data from ARCHER 1050 were presented today as an oral presentation [Abstract #9004] at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago and have been published simultaneously in the Journal of Clinical Oncology.

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"Overall survival is an important measure to assess efficacy of investigational compounds. These data presented today are particularly significant as dacomitinib is the first EGFR tyrosine kinase inhibitor in a Phase 3 head-to-head study comparing two tyrosine kinase inhibitors to show an improvement in overall survival," said Professor Tony Mok, Chair of Department of Clinical Oncology, The Chinese University of Hong Kong. "I look forward to having dacomitinib as a potential first-line treatment option for non-small cell lung cancer patients with EGFR-activating mutations."

Overall survival was a secondary endpoint of ARCHER 1050, a randomized, open label Phase 3 study comparing the efficacy and safety of dacomitinib to gefitinib for the first-line treatment of locally advanced or metastatic NSCLC in subjects with EGFR-activating mutations. At the OS data cutoff, median OS was 34.1 months with dacomitinib (95% CI: 29.5, 37.7) compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). Patients receiving dacomitinib had a 56.2 percent survival rate at 30 months compared with 46.3 percent for patients who received gefitinib. Subgroup analyses were consistent with the primary OS analysis across most baseline characteristics, including patients with common sub-mutations exon 19 and 21.

The adverse events (AEs) observed with dacomitinib in the study were consistent with findings from previous dacomitinib trials. The most common AEs were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%) and mouth sores (44%). The most common Grade 3 AEs with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 AEs occurred in two percent of dacomitinib-treated patients. There was one case of Grade 5 diarrhea and one case of Grade 5 liver disease. The discontinuation rate due to treatment-related AEs for dacomitinib was 10 percent compared to seven percent for gefitinib.

"What is most encouraging about these results is that patients with non-small cell lung cancer harboring EGFR-activating mutations who received dacomitinib achieved a median overall survival of nearly three years, a marked improvement compared to an established treatment in this setting," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "With today’s podium presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and the U.S. Food and Drug Administration Priority Review granted earlier this year, we are encouraged by these data and committed to deliver this promising investigational medicine to patients as quickly as possible."

In April 2018, the U.S. Food and Drug Administration (FDA) granted priority review for dacomitinib for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR-activating mutations. The FDA Prescription Drug User Fee Act (PDUFA) target action date is in September 2018. The European Medicines Agency also accepted the Marketing Authorization Application for dacomitinib for the same indication.

About Dacomitinib

Dacomitinib is an investigational, oral, once-daily, irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor (TKI). It has not received regulatory approval in any country.

In 2012, Pfizer and SFJ Pharmaceuticals entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites.

About Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer deaths worldwide.1 Non-small cell lung cancer (NSCLC) accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.2 Biomarker therapies dramatically changed the care of patients with metastatic NSCLC. Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.2,3,4

EGFR is a protein that helps cells grow and divide. When the EGFR protein is mutated it can cause cancer cells to form. EGFR mutations occur in 10 to 35 percent of NSCLC tumors globally, yet the disease is associated with low survival rates and disease progression remains a challenge.5,6

On June 4, 2018 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company") reported to confirm that it is involved in three poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)‘s (ASCO) (Free ASCO Whitepaper) Annual Meeting, in Chicago, Illinois taking place from 1 – 5 June (Press release, Immutep, JUN 4, 2018, View Source [SID1234527167]). All three posters relate to Immutep’s lead product candidate eftilagimod alpha ("efti" or "IMP321").

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Two of the posters (TPS1050 and TPS1109), were presented on June 2, and focused on the Company’s Phase IIb AIPAC (Active Immunotherapy PAClitaxel) double blind placebo trial evaluating the efficacy of efti in patients with metastatic breast cancer.

The first poster discussed the results from the safety run-in phase of the AIPAC trial, which have been previously announced to the market. This poster was presented by Prof. Duhoux, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain. Specifically, it reiterated that the overall response rate ("ORR") in patients to the combination of paclitaxel and efti was 47%, and that the disease control rate ("DCR") was 87%. It also noted that two of the responses to the combination therapy occurred relatively late in the treatment (after ~6 months) and that the safety run-in phase reported a very encouraging safety profile.

The second poster, presented by Dr. Dirix of GZA Hospitals Sint-Augustinus, Antwerp, Belgium, outlined the ongoing AIPAC trial, its design and primary end points.

The third poster (TPS3129) outlines the clinical trial design of the ongoing INSIGHT clinical trial, an open-labeled Phase I study to evaluate the feasibility and safety of intra-tumoral, intra-peritoneal, and subcutaneous injections with efti for advanced stage solid tumors. This is an investigator sponsored trial by Immutep’s partner, IKF in Frankfurt, Germany, which will be presented by the investigator on June 5 in Chicago.

The ASCO (Free ASCO Whitepaper) posters regarding the Company’s AIPAC trial can be accessed via the Immutep website under the Presentations tab at:

View Source

About the AIPAC clinical trial

The ongoing AIPAC (Active Immunotherapy PAClitaxel) Phase IIb clinical trial is a European multi-centre study evaluating eftilagimod alpha ("efti" or "IMP321") in combination with paclitaxel in metastatic breast cancer (clinicaltrials.gov identifier NCT 02614833). To date, 33 out of a planned 34 clinical sites across Belgium, the Netherlands, Poland, Hungary, United Kingdom, France and Germany are now actively recruiting and treating patients. The AIPAC study is currently expected to be fully recruited with 226 patients by the end of calendar 2018, with first Progression Free Survival data expected in calendar 2019.

About the INSIGHT clinical trial

The on-going INSIGHT Phase I clinical trial is an investigator initiated, explorative, single centre, open-label, study evaluating the feasibility and safety of intra-tumoural, intra-peritoneal, and subcutaneous injections of efti for advanced stage solid tumour entities (clinicaltrials.gov identifier NCT03252938). The Lead Investigator of this clinical trial is Professor Doctor Salah-Eddin Al-Batran, the Medical Director of the IKF.

On June 4, 2018 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported updated overall survival data from the Company’s pivotal Phase 2 trial of its targeted, high-specific-activity radiotherapeutic candidate, AZEDRA (iobenguane I 131), in patients with malignant, recurrent, or unresectable pheochromocytoma and paraganglioma (pheo/para), which is the subject of an oral presentation at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Progenics Pharmaceuticals, JUN 4, 2018, View Source [SID1234527185]).

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"This pivotal study, the largest prospective clinical trial in pheochromocytoma and paraganglioma to date, has demonstrated multiple clinical benefits of AZEDRA treatment, which has translated into impressive overall survival data in this highly pre-treated and advanced patient population," said Dr. Daniel Pryma, Associate Professor of Radiology & Radiation Oncology and Chief, Division of Nuclear Medicine & Clinical Molecular Imaging at the Perelman School of Medicine at the University of Pennsylvania, the trial’s lead investigator. "The primary cause of death in pheo/para patients is tumor progression. In this study, 98% of patients who received two doses experienced stable disease or better as measured by Response Evaluation Criteria In Solid Tumors (RECIST). In addition, 30% of pheo/para patients die from complications due to catecholamine-associated hypertension, while patients treated with AZEDRA were able to achieve control of catecholamine-associated hypertension and a sustained reduction of antihypertensive medications. These benefits were correlated with a robust tumor biomarker response. With no approved therapies in the U.S. for pheo and para, AZEDRA has the potential to offer a meaningful treatment option for patients with these life-threatening tumors."

Dr. Pryma will review the data today in an oral presentation entitled, "AZEDRA (iobenguane I 131) in patients with malignant, recurrent and/or unresectable pheochromocytoma or paraganglioma (PPGL): Updated efficacy and safety results from a multi-center, open-label, pivotal phase 2 study."

The pivotal phase 2 open-label, multi-center trial was conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). The trial met the primary endpoint evaluating the proportion of pheochromocytoma and paraganglioma patients who achieved a 50% or greater reduction of all antihypertensive medication for at least six months, and showed favorable results from a key secondary endpoint evaluating the proportion of patients with overall tumor response as measured by RECIST. 92.2% of patients treated with at least one therapeutic dose of AZEDRA achieved a confirmed partial response or stable disease by 12 months. AZEDRA was also shown to be safe and generally well tolerated.

Median overall survival time as of December 4, 2017 was 37 months from first AZEDRA therapeutic dosing in the overall study population, and 44 months among patients who received two therapeutic doses, compared to 18 months among patients who received only one therapeutic dose. The study data also suggest the potential for AZEDRA to extend survival in patients with liver or lung metastasis, which is generally considered in the literature to be less than 24 months. In this study, median survival time was similar in patients with lung or liver metastasis compared to those without (43 vs. 41 months). Long term follow-up continues.

"These data, which are the basis of our New Drug Application, show that AZEDRA has the potential to address the dual goals of therapy in pheo and para – to reduce the cardiovascular symptoms associated with the excess hormone production, and to produce favorable tumor responses," said Mark Baker, Chief Executive Officer of Progenics. "We are eagerly anticipating the FDA’s decision on AZEDRA, as we believe it has the potential to be a breakthrough treatment option for patients with these deadly, ultra-rare neuroendocrine cancers."

About AZEDRA

AZEDRA (iobenguane I 131) is a high-specific-activity radiotherapeutic product candidate in development as a treatment for malignant, recurrent, or unresectable pheochromocytoma and paraganglioma, which are rare neuroendocrine tumors of neural crest origin. AZEDRA is a substrate for norepinephrine reuptake transporter, which is highly expressed on the cell surface of neuroendocrine tumors. AZEDRA has been granted Orphan Drug designation, Fast Track status, and Breakthrough Therapy designation in the U.S. Under a SPA agreement with the FDA, a Phase 2 pivotal study has been completed in patients with malignant, recurrent, or unresectable pheochromocytoma and paraganglioma. The FDA granted Priority Review of Progenics’ New Drug Application and has set an action date of July 30, 2018 under the Prescription Drug User Fee Act. There are currently no FDA-approved therapies for the treatment of these ultra-rare diseases.

About Pheochromocytoma and Paraganglioma

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise from cells of the autonomic nervous system. Pheochromocytoma forms in the adrenal medulla, whereas paragangliomas form outside the adrenal gland. Standard treatment options for these tumors include surgery, palliative therapy and symptom management. Pheochromocytoma and paraganglioma tumors frequently secrete high levels of hormones that can lead to life-threatening hypertension, heart failure, and stroke in these patients. Malignant and recurrent pheochromocytoma and paraganglioma may result in unresectable disease with a poor prognosis, representing a significant management challenge with very limited treatment options and no approved anti-tumor therapies.

On June 4, 2018 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the publication of preclinical data elucidating the mechanism of action of APTO-253, the company’s clinical stage anticancer product candidate (Press release, Aptose Biosciences, JUN 4, 2018, View Source;p=RssLanding&cat=news&id=2352950 [SID1234527120]). The data are published in two separate articles in the June 2018 issue (Volume 17, Number 6) of Molecular Cancer Therapeutics, a peer-reviewed journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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The first publication, entitled "APTO-253 stabilizes G-quadruplex DNA, inhibits MYC expression and induces DNA damage in acute myeloid leukemia cells," demonstrates that the APTO-253 small molecule anticancer agent inhibits expression of the MYC oncogene and depletes cells of the MYC protein, triggers the DNA repair and stress response pathways, and promotes programmed cell death (apoptosis) in acute myeloid leukemia (AML) cell lines and fresh bone marrow samples derived from patients with AML and other hematologic malignancies that often depend on MYC upregulation. The data demonstrate a multifaceted mechanism of action for APTO-253, primarily through engagement of select G-quadruplex DNA structures, one of which is located in the promoter of the MYC gene and is uniquely suited to targeting hematopoietic malignancies.

MYC dysregulation is a common driver in many malignancies, making it an attractive therapeutic target. Repression of MYC expression by bromodomain (BET) inhibitors has proven effective at triggering apoptosis in leukemia cells; however, inhibition of bromodomain proteins can cause severe toxicities and myelosuppression. Unlike BET inhibitors and other cancer chemotherapies, APTO-253 acts through a distinct mechanism and does not cause toxicity to normal bone marrow cells, as demonstrated across various species, including humans. And, as a first in class MYC inhibitor that does not cause myelosuppression, APTO-253 may be particularly appropriate for management of patients having AML and other hematologic malignancies with compromised bone marrow function.

The second publication, entitled "APTO-253 is a new addition to the repertoire of drugs that can exploit DNA BRCA1/2 deficiency," expands on data from a poster presentation at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. This study identified a synthetic lethal interaction of APTO-253 in cancer cells deficient in BRCA1 or BRCA2 function, causing these cells to be hyper-sensitive to APTO-253. The research team found that APTO-253 stabilizes certain quadruplex DNA structures, which can elicit the DNA damage repair response and exhibit synthetic lethality comparable to olaparib – an FDA-approved targeted therapy that acts against cancers in people with hereditary BRCA1 or BRCA1 mutations, including some ovarian, breast and prostate cancers, although through a different mechanism. The findings revealed for APTO-253 potential new solid tumor indications in which patients with defined mutations can be genetically identified.

"These data provide new insights into the mechanism of action of APTO-253 and add to our knowledge of how this novel agent inhibits expression of the MYC gene, an oncogene that promotes tumor growth and resistance to drugs in AML and other cancers," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer.

About APTO-253

APTO-253 is a clinical-stage small molecule targeted therapeutic agent that inhibits expression of the MYC oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells, without causing general myelosuppression of the healthy bone marrow. The MYC oncogene is overexpressed in hematologic cancers, including acute myeloid leukemia (AML). Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or myelodysplastic syndromes (MDS). New findings reveal that APTO-253 might also serve certain solid tumor patients with BRCA1/2 mutations, but without causing toxicity to the normal bone marrow functions.

On June 4, 2018 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported that the U.S. Food and Drug Administration (FDA) has approved the Company’s Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for UCART22, Cellectis’ second wholly controlled TALEN gene-edited product candidate, for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) in adult patients (Press release, Cellectis, JUN 4, 2018, View Source [SID1234527136]).

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UCART22 is the 3rd allogeneic, off-the-shelf, gene-edited CAR T-cell product candidate approved by the FDA for clinical trials in the U.S., following UCART19 (exclusively licensed to Servier and under joint development agreement between Servier and Allogene), and Cellectis’ UCART123. Cellectis intends to begin the UCART22 Phase 1 study in the second half of 2018. The research for UCART22 will be led by Dr. Nitin Jain, Assistant Professor, and Prof. Hagop Kantarjian, Chairman in the Department of Leukemia and University Chair in Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston.

"The FDA’s approval of Cellectis’ UCART22 IND application for the treatment of B-ALL puts us one step closer to providing patients in need with a better access to an effective drug candidate for such a rare, devastating disease," said Prof. Stéphane Depil, Senior Vice President, Research & Development, and Chief Medical Officer, Cellectis. "With this opportunity, Cellectis is well-positioned to further its work in the off-the-shelf gene-editing space, in the hope of helping patients to beat B-ALL in the near future."

"Given that Cellectis is leading the allogeneic CAR-T approach across today’s medical landscape – first, with the FDA’s IND approval for UCART123 last year and now, with approval of UCART22 IND – we are eager to bring an innovative therapy to the market for patients who are suffering from B-ALL everywhere," added Stephan Reynier, Chief Regulatory and Compliance Officer, Cellectis. "The bottom line is that patients are in dire need of effective, affordable and easily accessible treatments across the board, and our off-the-shelf product candidates aim to do just that."

About UCART22

UCART22 is an allogeneic, off-the-shelf gene-edited T-cell product candidate designed for the treatment of B-ALL. Like CD19, CD22 is a cell surface antigen expressed from the pre-B-cell stage of development through mature B-cells. CD22 expression occurs in more than 90% of patients with B-ALL.[1]

UCART22 clinical trial is a Phase 1, open label dose-escalation and dose-expansion study to evaluate the safety, expansion, persistence and clinical activity of UCART22 (allogeneic engineered T-cells expressing anti-CD22 chimeric antigen receptor) in patients with relapsed or refractory CD22+ B-cell acute lymphoblastic leukemia (B-ALL). Dose level 1 to be administered is 1×105 UCART22 cells per kilogram. Dose levels 2 and 3 are respectively at 1×106 and 5×106.

ALL is a heterogeneous hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. It can start either with early B-cells or T-cells at different stages of maturity. The American Cancer Society’s estimates for acute lymphocytic leukemia (ALL) in the United States for 2018 (including both children and adults) are about 5,960 new cases of ALL and about 1,470 deaths from ALL. Approximately 85% of ALL cases involve precursor B-cells (B-ALL).

The manufacturing process of Cellectis’ allogeneic CAR T-cell product line, Universal CARTs or UCARTs, yields frozen, off-the-shelf, non-alloreactive engineered CAR T-cells. UCARTs are meant to be readily available CAR T-cells for a large patient population. Their production is industrialized with defined pharmaceutical release criteria