On June 4, 2019 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that the Company’s collaborators at Memorial Sloan Kettering Cancer Center (MSK), Prasad S. Adusumilli, M.D. and Michel Sadelain, M.D., Ph.D., presented an update on encouraging results from an ongoing MSK investigator-sponsored Phase 1 clinical study (NCT02414269) of a mesothelin-targeted CAR T immunotherapy for patients with mesothelin-associated malignant pleural solid tumors, primarily mesothelioma, who progressed following platinum-containing chemotherapy (Press release, Atara Biotherapeutics, JUN 4, 2019, View Source [SID1234536855]). Mesothelin-targeted, autologous CAR T cells delivered regionally were well-tolerated and showed encouraging anti-tumor activity in combination with pembrolizumab, a PD-1 checkpoint inhibitor. The findings were presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2019 in Chicago.

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 updates to this study presented by our MSK collaborators reaffirm mesothelin as a promising target for patients with advanced mesothelioma and establishes an important proof-of-concept advancement for CAR T immunotherapy in solid tumors," said Christopher Haqq, M.D., Ph.D., Executive Vice President and Chief Scientific Officer of Atara Biotherapeutics. "Based on these continued encouraging safety results and anti-tumor responses, Atara recently prioritized our mesothelin-targeted CAR T program and anticipate autologous ATA2271 will be Atara’s first next-generation CAR T IND in advanced mesothelioma."

The MSK Phase 1 clinical study has recruited 27 patients, 25 with malignant pleural mesothelioma (MPM), one with metastatic lung cancer and one with metastatic breast cancer, who had a median of 3 prior treatment regimens, to evaluate the safety and potential anti-tumor activity of a CD28-costimulated, mesothelin-targeted autologous CAR T immunotherapy. The study added two higher dose cohorts to the six-dose cohorts reported in March 2019 with administration directly to the tumor site. Twenty-two of the 27 patients were subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor.

Mesothelin-targeted, autologous CAR T administration was found to be generally well tolerated, with no CAR T-related toxicities higher than grade 2 observed based on monitoring multiple clinical, radiological, and laboratory parameters.

In a subset of 16 MPM patients who also received lymphodepleting chemotherapy and at least 3 doses of pembrolizumab with a minimum follow-up of 3 months following the final dose of PD-1, the 12-month overall survival (OS) was 80% and best overall response rate (ORR) was 63% (10 of 16), consisting of 3 durable investigator-assessed complete responses (CR) and seven partial responses (PR). Eleven of the 16 patients in this subset were programmed cell death ligand 1 (PD-L1) negative, defined as undetectable expression of PD-L1 in tumor cells by immunohistochemistry, with 6 of the 10 total responses observed in PD-L1 negative patients (1 CR and 5 PR). CAR T cells persisted in the pleural fluid and trafficked to the peripheral blood in these 16 patients for up to 42 weeks.

Following progression on standard platinum-containing chemotherapy, the expected 12-month OS, median OS and ORR for patients with MPM treated with a PD-1 containing regimen is 63%, 11-18 months and 5%-29%, respectively.1-5

MSK is also investigating mesothelin-targeted CAR T cells for patients with mesothelin-associated advanced breast cancer (NCT02792114). Additional results from these ongoing studies are expected to be presented at upcoming scientific congresses.

Abstract 2511: Regional delivery of mesothelin-targeted CAR T cells for pleural cancers: Safety and preliminary efficacy in combination with anti-PD-1 agent
Oral Presentation Date and Time:Tuesday, June 4, 2019, 8:36 a.m. – 8:48 a.m. CDT
Session Title: The Who, What, and Where of CAR T
Location: S406, McCormick Place, South Building, Chicago, IL
Authors:Prasad S. Adusumilli, Marjorie G Zauderer, Valerie W Rusch, Roisin E O’Cearbhaill, Amy Zhu, Daniel Ngai, Erin McGee, Navin Chintala, John Messinger, Waseem Cheema, Elizabeth F Halton, Claudia R Diamonte, John Pineda, Alain Vincent, Shanu Modi, Steve Solomon, David R Jones, Renier J Brentjens, Isabelle C Riviere, Michel W Sadelain
Affiliations:Memorial Sloan Kettering Cancer Center

On June 4, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported new data from the ongoing pivotal Phase 3 SIERRA study of Iomab-B’s single agent effect in patients with active, relapsed or refractory AML or Acute Myeloid Leukemia age 55 and above (Press release, Actinium Pharmaceuticals, JUN 4, 2019, View Source [SID1234536852]). The data was presented by SIERRA investigator Benjamin Tomlinson, M.D., Adult Hematologic and Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center (Cleveland, OH) in a poster presentation at the 2019 ASCO (Free ASCO Whitepaper) or American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting that is being held from May 31st – June 4th at the McCormick Place, Chicago.

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!

Dr. Tomlinson, said, "Older patients with active, relapsed or refractory AML are an underserved patient population. These patients, particularly those with high blast counts as seen in the SIERRA trial, are not typically considered candidates for transplant, which is a potentially curative treatment for AML, and have a poor prognosis with other therapeutic options. Iomab-B has uniquely demonstrated an ability to effectively condition these patients for transplant with robust engraftment. We hypothesized that this successful engraftment is due to the myeloablation and anti-leukemic effect of Iomab-B, since these patients had a median of 30% bone marrow blasts prior to transplant. Therefore, we are highly encouraged to observe that Iomab-B as a single agent has a significant anti-leukemic effect and rapidly reduces peripheral blasts."

The poster can be accessed on Actinium’s website (Click Here).

The poster evaluated data from the first 25% of patients (38) from the SIERRA trial where a total of 29 patients received Iomab-B. This included 19 patients who received Iomab-B directly and 10 patients who received Iomab-B via crossover after conventional care salvage chemotherapy failed to produce a complete response. Previously presented preliminary feasibility data from the SIERRA trial demonstrated that all patients receiving Iomab-B had robust BMT or Bone Marrow Transplant donor engraftment and donor chimerism without delay. The new data presented at ASCO (Free ASCO Whitepaper) evaluated Iomab-B’s effect as a single agent on white blood cells, lymphocytes and peripheral blasts. Of the 16 patients for whom data was available, there was a median reduction of peripheral blasts of 98% by day 3 and 100% reduction by day 8 following Iomab-B administration and prior to any other pre-BMT conditioning. Rapid reduction of peripheral blasts has been observed as an independent prognostic marker that is predictive of both CR or Complete Response and RFS or Relapse-Free Survival in patients with AML after receiving cytotoxic chemotherapy. Gianfaldoni et al1 performed an analysis of 30 newly diagnosed AML patients who were treated with cytotoxic induction chemotherapy and found that a rapid reduction of peripheral leukemia blasts correlated with responses and all patients that achieved CR had a rapid reduction of their peripheral blasts. Elliot et al2, performed a retrospective analysis of 86 adult patients with AML and identified time to clearance of circulating leukemia blasts as an independent prognostic marker of RFS that superseded all other known risk factors including karyotype and number of cycles of induction therapy needed to achieve CR.

"We are delighted that Iomab-B continues to generate encouraging data in the SIERRA trial," said Dr. Mark Berger, Actinium’s Chief Medical Officer. "This is the first time single agent Iomab-B clinical data has been presented and we are quite excited by the rapid peripheral blast reduction that has been observed thus far. Peripheral blast reduction is a highly relevant clinical measure and we are optimistic that it will have a positive impact on durable complete response rates, which is the primary endpoint of the SIERRA trial. We are confident that this data will be well received by SIERRA investigators and will add to the strong engraftment data that has been already reported at ASH (Free ASH Whitepaper) and TCT. Collectively, we are encouraged that Iomab-B is continuing to exemplify best-in-class transplant conditioning potential for this difficult to treat patient population."

Sources:

1) Gianfaldoni et al. clearance of leukemic blasts from peripheral blood during standard induction treatment predicts the bone marrow response in acute myeloid leukemia: a pilot study. British Journal of Haematology, 2006 March 16; 134, 54-57.

2) Elliott et al. Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood. 2007 Dec 15; 110(13):4172-4. Epub 2007 Oct 1.

About Iomab-B

Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the anti-CD45 antibody apamistamab and the radioisotope iodine-131 that is intended to be a re-induction and conditioning agent prior to a BMT or bone marrow transplant. Iomab-B was developed at the Fred Hutchinson Cancer Research Center and has been studied in over 300 patients in multiple hematologic indications across 12 clinical trials in addition to the ongoing SIERRA study in older patients with active, relapsed or refractory AML or Acute Myeloid Leukemia prior to patients receiving an allogeneic BMT or bone marrow transplant. Iomab-B is Actinium’s lead targeting conditioning ARC in its multi-target, multi-indication targeted conditioning pipeline that includes the Iomab-B and Actimab-MDS programs for BMT and the Iomab-ACT program that will study a lower dose of Iomab-B for lymphodepletion prior to CAR-T and other cellular therapies.

About Actinium Pharmaceuticals, Inc.

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium

On June 3, 2019 Nordic Nanovector ASA (OSE: NANO) reported that the European Patent Organisation (EPO) has granted the company’s European Patent covering the use of Betalutin or Humalutin in combination with anti-CD20 antibodies for the treatment of non-Hodgkin’s lymphoma (NHL) (Press release, Nordic Nanovector, JUN 3, 2019, View Source [SID1234553449]). The same patent has also been issued in Japan, China, Australia, Hong Kong, Israel, Russia and Singapore while the patent is pending in USA, Brazil, Canada, Indonesia, India, Korea, Mexico, New Zealand, Philippines, Ukraine and South Africa.

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!

This patent is a result of Nordic Nanovector’s continued focus on securing intellectual property rights on its pipeline of novel CD37-targeting drug candidates.

Patents covering Betalutin and Humalutin, as well as their medical applications have already been granted in Europe, USA, Canada, China, Hong Kong, Australia, Indonesia, Israel, Japan, Korea, Mexico, New Zealand, Philippines, Russia, Singapore, Ukraine and South Africa. India, Brazil and Thailand are expected to be granted soon.

Finally, two newer patent applications related to Betalutin’s clinical applications and combination with other drugs have also been filed. The latest application has been made public on the 31 May under WO/2019/101789.

On June 3, 2019 Ascentage Pharma, a globally-focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, hepatitis B virus and age-related diseases, reported that the company presented new data of two apoptosis-targeted drug candidates APG-115 (a novel MDM2-p53 inhibitor) and APG-1387 (a novel IAP inhibitor) at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Ascentage Pharma, JUN 3, 2019, View Source [SID1234536846]).

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!

With the theme "Caring for Every Patient, Learning from Every Patient", 2019 ASCO (Free ASCO Whitepaper) Annual Meeting attracted over 40,000 oncologists and researchers globally to present and share the cutting-edge research and achievements in clinical oncology in Chicago from May 31-June 4.

Ascentage Pharma presented the data from its most recent clinical trials of APG-115 in China and U.S. (Board #118 and #116), and the data of phase I study of APG-1387 as a monotherapy or in combination with pembrolizumab in treatments of patients with advanced solid tumors (Board #117).

It is encouraging that in the study of APG-115 as a monotherapy, a confirmed PR was observed in 1 patient with liposarcoma (TP53-WT and MDM2Amp), with target lesion decreased 64%.

"Liposarcoma is a common histological type of malignant soft tissue sarcomas, accounting for about 15% of soft tissue sarcomas. There is no effective treatment for it and the probability of recurrence is high. Liposarcoma belongs to the ‘cold tumor’ type and has a poor response to immunotherapy," said Pro. Xing Zhang, Chief physician of Melanoma and Sarcoma Medical Oncology Unit of Sun Yat-sen University Cancer Center. She continued, "We believe APG-115 is an efficient MDM2-p53 inhibitor. The data of Phase I study of APG-115 in Chinese patients with liposarcomas is encouraging. We enrolled 14 patients, 8 with liposarcoma; a confirmed PR was observed in one liposarcoma patient after 4 months of treatment discontinuance. Another 5 patients achieved SD (including 2 liposarcoma patients). Based on clinical trial results, APG-115 is well-tolerated and with acceptable safety profile. We expect further data to address the unmet medical needs."

There have also been promising advances in the Phase I study of a novel IAP inhibitor, APG-1387, as a monotherapy in treatments of patients with advanced solid tumors. Drew W. Rasco, M.D., Associate Director of Clinical Research at the START Center for Cancer Care in San Antonio commented: "Among 10 mPC (metastatic pancreatic cancer) patients treated with APG-1387 monotherapy, 3 patients achieved SD. One patient at MTD received SD for >9 cycles (3-wk a cycle) with the best response +6%, still ongoing; one patient achieved SD for > 8 months with best response of -16.7% tumor shrinkage. This preliminary result is worth mentioning, because mPC patients in general have only 3-6 months survival time, and overall survival rate of one year is 8.8%. Currently there is no effective treatment. We look forward to additional data from the on-going studies."

"APG-115 and APG-1387 are two apoptosis targeting products in clinical development of Ascentage Pharma. These results show our further progress in clinical development of targeting apoptosis. We are working hard to provide more therapy options for patients as soon as possible," said Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma.

– A Phase I Study of a Novel MDM2-P53 Antagonist APG-115 in Chinese Patients with Advanced Solid Tumors

Through April 23, 2019, 14 patients with advanced solid tumors (8 LPSs) received APG-115 ranging from 100-200mg, QOD, 3 weeks on 1 week off, in a 4-week cycle.
Two DLTs judged by investigator at 200mg (thrombocytopenia and febrile neutropenia). APG-115 was well-tolerated across all dose levels tested and the MTD was 150mg, due to the late onset thrombocytopenia, safety expansion was ongoing at 100mg. The most common Grade ≥3 AEs were hematologic toxicities, particularly thrombocytopenia, which were predictable as the activation of p53 in the bone marrow.
APG-115 displayed approximately linear pharmacokinetics over 100-200mg range.
A confirmed PR was observed in 1 patient with liposarcoma (TP53-WT and MDM2Amp) at the 150mg, and the duration of response has lasted after 4 months of treatment discontinuance.
– A Phase I study of a Novel MDM2 Antagonist APG-115 in Patients with Advanced Solid Tumors

Through April 19, 2019, total 29 patients were treated with APG-115 at various doses range from 10-300mg.
Most common TRAEs (>10%): fatigue, nausea, vomiting, decreased appetite, diarrhea, neutrophil count decreased, platelet count decreased, white blood cell count decreased.
Platelet count decreased, fatigue, and nausea were determined as DLTs.
APG-115 at 100mg QOD (3 weeks on, 1 week off) was well-tolerated. The MTD/RP2D of APG-115 monotherapy was determined as 100mg.
Base on the preliminary anti-tumor data, APG-115 is active. Nine patients achieved SD among 19 response evaluable patients. 50% (5/10) patients at MTD achieved SD among response evaluable patients.
PK analyses have shown that AUC and Cmax generally increase dose proportionally over the dose range of 20-300mg.
Serum MIC-1 (biomarker of TP53 activation) increase was exposure dependent within the dose range tested in patients with solid tumors.
Further evaluation of APG-115 in combination with pembrolizumab in patients with advanced solid tumors is ongoing.
– A Phase I Study of a Novel IAP Inhibitor APG-1387 as a Monotherapy or in Combination with Pembrolizumab in Treatments of Patients with Advanced Solid Tumors

Through April 19, 2019, 24 patients had been treated with APG-1387 and 5 patients had been treated with APG-1387 plus pembrolizumab.
APG-1387 was well tolerated and had manageable adverse events. Most common TRAEs (>10%) are fatigue.
Two DLTs were observed at 60mg including lipase increase and facial nerve disorder, MTD of APG-1387 monotherapy was determined as 45mg.
Three out of 10 mPC patients in APG-1387 monotherapy (at 45mg) achieved SD, one of them at 45 mg has been treated > 9 cycles with confirmed SD (+6%).
Preliminary PK data of APG-1387 showed a dose proportionality in exposure (Cmax and AUC) over the dose range of 20-45 mg.
APG-1387 treatment induced significant XIAP suppression in PBMCs and cytokine (especially IL-12p40 and IL-10) release in serum, suggesting a potential pharmacodynamics and host immunomodulation effects.
The potential effects of APG-1387 alone or in combination with pembrolizumab deserve further exploration in patients with advanced pancreatic cancer.
About APG-115

APG-115 is an orally administered, selective, small molecule inhibitor of the MDM2-p53 PPI. APG-115 has strong binding affinity to MDM2 and is designed to activate p53 tumor suppression activity by blocking the MDM2-p53 PPI. APG-115 is currently in Phase I clinical trials in China and the United States in patients with ACC (Adenoid cystic carcinoma) and other sarcomas. APG-115 is in Phase Ib/II combination study with pembrolizumab in the U.S.

About APG-1387

APG-1387 is a novel small molecule IAP inhibitor (Inhibitor of Apoptosis Protein). Ascentage Pharma is developing APG-1387 globally, and has completed dose escalation Phase I clinical trials in advanced solid tumors in China and Australia, and a Phase I clinical trial of APG-1387 and pembrolizumab combination is currently ongoing in the U.S. APG-1387 is also being investigated for the treatment of patients with chronic hepatitis B virus in China.

On June 3, 2019 ImmunityBio , a privately held immunotherapy company at late stage clinical development, that aims to synergistically deploy a broad portfolio of biological molecules as an integrated cancer vaccine platform targeting multiple tumor types without the use of high-dose chemotherapy, reported that Dr. Patrick Soon-Shiong will be presenting at the Jefferies 2019 Annual Healthcare Conference being held in New York City from June 4th-7th 2019 (Press release, ImmunityBio, JUN 3, 2019, View Source [SID1234542351]). The presentation and one-on-one discussions will launch the privately held company with a portfolio of over 20 first in class biological molecules deployed to orchestrate the innate and adaptive immune system, and will feature clinical updates of multiple trials with registrational intent.

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!

Conference Details:

Event: Jefferies 2019 Annual Healthcare Conference

Date/Time: Tuesday, June 4, 2019, Presentation at 8:00am ET

Location: New York, NY

For more information regarding ImmunityBio please visit www.ImmunityBio.com