On December 7, 2020 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, reported that it has been notified by the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on patient enrollment and dosing in an ongoing Phase 1/2 dose-escalation clinical trial evaluating BPX-601 in patients with previously treated metastatic pancreatic or prostate cancer (Press release, Bellicum Pharmaceuticals, DEC 7, 2020, View Source [SID1234572350]). The FDA is taking this action due to the death of a pancreatic cancer patient in the trial reported to the agency by the company. The clinical investigator and Bellicum classified the patient death as unrelated to BPX-601 and rimiducid.

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The company plans to work diligently with the FDA to address the agency’s questions and fulfill the requirements for resuming the trial. The clinical hold does not affect the company’s plans to initiate enrollment in the Phase 1/2 clinical trial of BPX-603, a dual switch GoCAR-T, in patients with HER2+ solid tumors by the end of the year.

About BPX-601

BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence, production of immunomodulatory cytokines and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for pancreatic and prostate tumors expressing prostate stem cell antigen (PSCA).

On December 7, 2020 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that interim data from its ongoing Actimab-A CLAG-M Phase 1 combination trial in relapsed or refractory Acute Myeloid Leukemia (AML) were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Press release, Actinium Pharmaceuticals, DEC 7, 2020, View Source [SID1234572348]).

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ASH Oral Presentation: A Phase I study of Lintuzumab Ac225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML

In the third and planned final dose cohort of Actimab-A CLAG-M, 100% of evaluable patients achieved remission. The trial, which is being conducted at the Medical College of Wisconsin (MCW), is advancing to a fourth dose cohort of 1.0 μCi/kg. Across the first three cohorts, 67% (10/15) patients treated with 0.25, 0.50 and 0.75 μCi/kg of Actimab-A and the standard regimen of CLAG-M achieved a Complete Remission (CR) or Complete Remission with inadequate hematopoietic recovery (CRi). Further, 83% of patients (10/12) who received 3 or fewer prior lines of treatment achieved CR or CRi. Notably, 70% of CR/CRi patients were MRD (Measurable Residual Disease) negative indicating a deep remission with no detectable disease. MRD negativity is defined as ≤0.1% AML cells. These results, which include subtherapeutic doses of Actimab-A in the first two dose cohorts, represent a marked improvement over CLAG-M treatment alone (ORR: 55%, MRD negativity: 39%) implying potential mechanistic synergy. This novel Phase 1 combination trial is for patients with relapsed or refractory acute myeloid leukemia (R/R AML) age 18 and above deemed medically fit for cytotoxic chemotherapy.

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "We look forward to continuing our work with the investigators at MCW in the Actimab-A CLAG-M combination trial. Thus far we remain thrilled with the high rates of remission, MRD negativity and transplant in this trial, which highlights the potential this combination may have for patients with R/R AML. It is exciting to see the profile of this combination emerge not only for therapeutic purposes but also for its potential as a bridge to transplant as noted by the investigators at MCW. Our CD33 program is focused on exploring the synergistic effects of Actimab-A with other therapeutic modalities and evaluating these combinations as potential backbone therapies in R/R AML."

About Actinium’s CD33 Program

Actinium’s CD33 program is evaluating the clinical utility of Actimab-A, an Antibody Radiation Conjugate (ARC) comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as patients with multiple myeloma. The CD33 development program is driven by data from over one hundred treated patients, including a Phase 1/2 trial where Actimab-A produced a remission rate as high as 69% as a single agent. This clinical data is shaping a two-pronged approach for the CD33 program, where at low doses the Company is exploring its use for therapeutic purposes in combination with other modalities and at high doses for use for targeted conditioning prior to bone marrow transplant. Actinium currently has multiple clinical trials ongoing including the Phase 1 Actimab-A CLAG-M and Phase 1/2 Actimab-A venetoclax combination trials and is exploring additional CD33 ARC combinations with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.

On December 7, 2020 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a pioneer in T-cell immunotherapy, leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with serious diseases including solid tumors, hematologic cancers and autoimmune disease, reported the presentation of the first preclinical evaluation of ATA3219, a next-generation, off-the-shelf, allogeneic CAR T-cell therapy targeting CD19, as well as data supporting its multicohort Phase II study with tab-cel (tabelecleucel) for the treatment of rare EBV-driven diseases (ATA129-EBV-205) (Press release, Atara Biotherapeutics, DEC 7, 2020, View Source [SID1234572347]). These data are being featured in five poster presentations at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 5-8, 2020.

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"Though the current generation of CD19 CAR T immunotherapies has transformed how we treat hematologic malignancies, a significant opportunity remains to improve outcomes and make the power of CAR T accessible to more patients using allogeneic cells with our differentiated EBV T-cell platform," said Jakob Dupont, M.D., Executive Vice President and Global Head of Research and Development at Atara. "As a leader in allogeneic CAR T-cell therapy, Atara is developing ATA3219 to be best-in-class, improving upon established CD19 targeting by leveraging both our EBV T-cell platform and novel 1XX co-stimulation signaling technology. We are pleased to share, for the first time, preclinical data demonstrating the antitumor activity, persistence, polyfunctional phenotype and safety of ATA3219."

Preclinical results presented at ASH (Free ASH Whitepaper) detail findings from in vitro and in vivo evaluations of ATA3219. Specifically, in vitro functional studies demonstrate potent antitumor activity of ATA3219 against CD19-expressing target lines, with durable CD19 antigen-specific and HLA-independent killing of CD19 targets. In addition, both in vivo and in vitro assessments of ATA3219 alloreactivity support a potentially favorable safety profile that would be required for an allogeneic, off-the-shelf CAR-T therapy.

Furthermore, in vivo, ATA3219 demonstrates potent antitumor activity in an established disseminated tumor model of acute lymphoblastic leukemia and is associated with long-term persistence and survival benefit. No treatment-related toxicities were observed in this animal model. Together, these findings support advancing ATA3219 to clinical evaluation.

ATA3219 combines an allogeneic EBV T-cell approach with a CAR signaling domain designed to improve upon current and clinically validated CD19 targeted CAR therapies without the need for gene editing. ATA3219 utilizes next-generation 1XX co-stimulatory domain technology, designed to extend functional persistence without compromising potency.

Following a successful pre-investigational new drug (IND) meeting with the U.S. Food and Drug Administration (FDA) in early Q4 2020, Atara plans to submit an IND for ATA3219 in 2021.

Additionally, Atara will report several data sets related to lead product candidate tab-cel including the first-ever presentation of data on patients with life-threatening complications associated with EBV viremia.

In this heterogeneous group of patients with life-threatening complications stemming from EBV viremia including some with hemophagocytic lymphohistiocytosis (HLH), a condition with poor prognosis for which treatment options are limited, 80 percent (n=4/5) of patients in the EAP-201 study with persistent EBV viremia (not HLH or chronic active EBV (CAEBV) were responders, and 50 percent (n=2/4) of the patients in EAP-901 with EBV viremia and HLH were responders. The overall survival (OS) rate at one year in patients with EBV viremia treated in the EAP-201 study was 100 percent for a median follow-up of 14.6 months (min 12.2, max 17.8).

Tab-cel was generally well-tolerated with no new safety signals in this study and data support the continued overall safety profile of the product. The EAP-901 study reported a fatal SAE of chronic hepatic failure that was assessed as unrelated to treatment; one patient experienced a grade 3 TESAE of facial nerve disorder that was assessed as possibly related to treatment and recovered in one month. There were no other fatal or treatment-related TESAEs reported in this patient population.

The Company has now presented clinical data for tab-cel in all six of the patient populations of the multi-cohort study, showing meaningful efficacy and consistent favorable safety profile.

In a poster evaluating the Healthcare Resource Utilization (HRU) and cost for patients with post-transplant lymphoproliferative disease (PTLD) following kidney transplant, it was found that PTLD is associated with substantial HRU and cost (>$200k PPY in the year diagnosed), regardless of the year diagnosed post-transplant, while patients without PTLD and patients who haven’t developed PTLD had a cost of ~$83k per-person year (PPY) in year one, and ~$26k PPY for year two and three post-transplant. Patients who developed PTLD continued to incur higher healthcare costs than patients who did not develop PTLD in years beyond the PTLD diagnosis year.

"We are pleased to see the growing body of evidence showing that tab-cel was well-tolerated and demonstrated strong objective response rates and overall survival in patients with life-threatening EBV-driven diseases beyond EBV+ PTLD," said AJ Joshi, M.D., Senior Vice President and Chief Medical Officer at Atara. "These data support the continued study of tab-cel in the multicohort trial aligned with our mission of bringing potentially transformative therapies to patients with serious diseases of high unmet medical need. Additionally, the characterization of the significant cost burden of PTLD begins to clarify important aspects of the significant value that a transformative treatment could provide to patients and the healthcare system."

Atara Poster Presentations at ASH (Free ASH Whitepaper):

Title: ATA3219: A Potent Next-Generation Allogeneic Off-the-Shelf CD19-CAR T Therapy without the Need for Gene-Editing
Abstract #: 3259
Session: 703. Adoptive Immunotherapy: Mechanisms and New Approaches: Poster III
Time and Location: Monday, December 7, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: Clinical Experience of Tabelecleucel in Patients with Life-Threatening Complications of Epstein-Barr Virus Viremia
Abstract #: 2554
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster II
Time and Location: Sunday, December 6, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: Clinical Experience of Tabelecleucel in Patients with EBV+ Primary (PID) or Acquired Immunodeficiency (AID) Associated Lymphoproliferative Disease
Abstract #: 1658
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster I
Time and Location: Saturday, December 5, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: High Healthcare Resource Utilization and Cost for PTLD Patients Following Kidney Transplants
Abstract #: 3482
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster III
Time and Location: Monday, December 7, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

Title: A Multicenter, Multicohort, Open-Label, Single-Arm per Cohort, Phase II Study to Assess the Efficacy and Safety of Tabelecleucel in Patients with EBV-Associated Diseases Using an Adaptive Two-Stage Study Design
Abstract #: 2551
Session: 905. Outcomes Research—Malignant Conditions (Lymphoid Disease): Poster II
Time and Location: Sunday, December 6, 2020: 7:00 AM-3:30 PM ET, Poster Hall (Virtual Meeting)

On December 7, 2020 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that it will hold a conference call on Wednesday, December 9, 2020 at 10:00 a.m. ET to discuss clinical data from ongoing studies evaluating eganelisib in triple negative breast cancer (TNBC) which will be presented during the San Antonio Breast Cancer Symposium (SABCS) being held virtually, December 8-11, 2020 (Press release, Infinity Pharmaceuticals, DEC 7, 2020, View Source [SID1234572346]).

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Conference Call Information

A live webcast of the conference call can be accessed in the "Investors/Media" section of Infinity’s website at www.infi.com. To participate in the conference call, please dial (877) 316-5293 (domestic) and (631) 291-4526 (international) five minutes prior to start time. The conference ID number is 2088322. An archived version of the webcast will be available on Infinity’s website for 30 days.

Presentation Details:

Title: MARIO-3 phase II study initial data evaluating a novel triplet combination of eganelisib (IPI-549), atezolizumab (atezo), and nab-paclitaxel (nab-pac) as first-line (1L) therapy for locally advanced or metastatic triple-negative breast cancer (TNBC)

Presenter: Erika Hamilton, M.D., Tennessee Oncology

Date: Wednesday, December 9, 2020, 8:00 a.m. CT

Abstract: PS11-32

Poster Session: 11

Title: ARC-2: Efficacy and safety of etrumadenant (AB928) + pegylated liposomal doxorubicin (PLD) ± eganelisib (IPI-549) in participants with metastatic ovarian and triple negative breast cancer

Date: Wednesday, December 9, 2020, 8:00 a.m. CT

Abstract: PS12-12

Poster Session: 12

On December 7, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported updated results from a dose expansion study of tebotelimab, an investigational, bispecific PD-1 × LAG-3 DART molecule, in patients with diffuse large B-cell lymphoma (DLBCL) (Press release, MacroGenics, DEC 7, 2020, View Source [SID1234572345]). The data were presented at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 5-8, 2020.

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LAG-3 has been shown to be highly expressed in DLBCL and has emerged as a therapeutic target of interest in this population, while PD-1-targeted therapy has yielded modest efficacy. There remains significant unmet need for patients with relapsed/refractory (R/R) DLBCL.

In one of the tebotelimab monotherapy dose expansion cohorts, 20 DLBCL patients were enrolled, half of whom were CAR T cell therapy experienced. As of the October 23, 2020 data cut-off, there were 13 response-evaluable patients.

A preliminary objective response rate (ORR) of 53.8% (7 of 13 patients) was observed, including responses in five of seven CAR T cell-naïve patients and in two of six CAR T cell experienced patients, the latter of whom both had complete responses. A preliminary duration of response of up to 168 days was observed, with six of seven ongoing responses as of the cut-off date. In the study, baseline LAG-3 expression appeared to associate with clinical response, with additional analyses ongoing.

Tebotelimab was generally well-tolerated among heavily pre-treated R/R DLBCL patients, with manageable infusion-related reactions and no evidence of tumor lysis syndrome. The most common TRAE was pyrexia, which occurred in three (15%) patients. A single Grade 3 TRAE of anemia was observed.

"Although early, the preliminary ORR observed in relapsed/refractory DLBCL patients treated with tebotelimab is promising," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "Beyond our continued enrollment of patients in the combination study of tebotelimab in solid tumors, we look forward to presenting data from the full cohort of the 20 enrolled DLBCL patients, as well as potentially defining a future registration path for this DART molecule."

About Diffuse Large B-Cell Lymphoma

DLBCL is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 25 percent of NHL cases globally. According to published research, the incidence in the U.S. and England is approximately 7 cases per 100,000 persons per year, with a median age at presentation of 64 years. DLBCL represents a heterogeneous group of tumors consisting of large, transformed B cells with prominent nucleoli and basophilic cytoplasm, a diffuse growth pattern, and a high proliferation fraction. While DLBCL is curable in approximately half of cases with current therapy, particularly those who achieve a complete remission with first-line treatment, significant unmet medical need remains for patients with relapsed or refractory disease.

About Tebotelimab

Tebotelimab (previously known as MGD013) is an investigational, first-in-class bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab has been engineered to concomitantly or independently bind to PD-1 and LAG-3 and disrupt these non-redundant inhibitory pathways to further restore exhausted T-cell function. Tebotelimab is being evaluated in a Phase 1 dose expansion study as monotherapy in several tumor types, including both solid tumors and hematological malignancies, and in combination with margetuximab, an investigational Fc-engineered monoclonal antibody targeting HER-2, in three cohorts of patients with advanced HER2-positive cancers (NCT03219268). Tebotelimab will also be evaluated in combination with margetuximab and chemotherapy as part of the ongoing Phase 2/3 MAHOGANY study in patients with HER2-positive gastric or gastroesophageal junction cancer (NCT04082364). MacroGenics’ regional partner in Greater China, Zai Lab, participates in the MAHOGANY study and is also evaluating tebotelimab independently in Phase 1 combination studies with niraparib, a PARP inhibitor, and brivanib, a dual target tyrosine kinase inhibitor of the VEGF and FGF receptors, for the study of advanced gastric cancer and hepatocellular carcinoma, respectively.