On September 16, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported Mr. Jarrod Longcor, chief business officer of Cellectar presented data from Cohort 6 of its Phase 1 dose escalation study of CLR 131 in relapsed or refractory multiple myeloma (R/R MM), in a late breaker poster at the 17th International Myeloma Workshop being held in Boston, MA from September 12-15, 2019 (Press release, Cellectar Biosciences, SEP 16, 2019, View Source [SID1234539546]).

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The poster, entitled: "CLR 131 Demonstrates High Rate of Activity in a Phase 1, Dose Escalation Study in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)" highlights data from 4 subjects in Cohort 6 who received a fractionated dose of 37.5 mCi/m2. Subjects in this cohort achieved a 50% overall response rate, with two subjects achieving a partial response and two subjects achieving minimal responses (39% and 48% reduction in M protein). CLR 131 was deemed safe and tolerated in all subjects with cytopenias being the only reported treatment emergent adverse events of grade 3 or higher. The majority (75%) of the subjects had high risk cytogenetics where median bone marrow plasma cell involvement was 25%. Patients’ median age was 72.5 and averaged 5 prior systemic therapies, with one patient being dual class refractory, one being quad-refractory, and two being penta-refractory.

The Phase 1 study employs the International Myeloma Working Group (IMWG) criteria for measuring responses. The IMWG defines a partial response as a 50% reduction in the marker of disease and a minimal response as a 25% to 49.9% reduction.

"Cohort 6’s overall response rate of 50% with 100% disease control in highly chemo-refractory elderly patients highlights CLR 131’s potential as a first-in-class targeted radiotherapeutic for relapsed or refractory multiple myeloma. We saw an encouraging dose response compared to prior cohorts and CLR 131 continues to demonstrate a favorable safety profile," said James Caruso, president and CEO of Cellectar. "We have progressed to a higher 40 mCi/m2 fractionated dose Cohort 7, with data expected in Q4 2019. Additionally, based on the positive results from Cohort 6, we are now allowed to use the 37.5 mCi/m2 dosing level in our ongoing Phase 2 (CLOVER-1) study evaluating CLR 131 in patients with relapsed/refractory (R/R) B-cell malignancies and expect data from the Phase 2 trial in Q4 2019."

About the Phase 1 R/R MM Trial

The Phase 1 multicenter, open-label, dose-escalation study is designed to evaluate the safety and tolerability of CLR 131 administered as a 30-minute IV infusion, either as a single bolus dose or as two fractionated doses, in patients with R/R MM. All doses to date have been deemed safe and well tolerated by an independent Data Monitoring Committee (DMC). Based on the data and the recommendation of the DMC, the Company has initiated a Cohort 7 where patients will receive 40mCi/m2 fractionated dose of CLR 131.

Based upon the encouraging activity from the 37.5 mCi/m2 fractionated dose of CLR 131 in Cohort 6, the company is evaluating this dose level in a larger population in its Phase 2 (CLOVER-1) trial as well.

A copy of the poster presentation and materials can be accessed on the Posters and Publications section of the Cellectar website.

About CLR 131

CLR 131 is a small-molecule, cancer-targeting radiotherapeutic Phospholipid Drug ConjugateTM (PDC) designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. CLR 131 is the company’s lead therapeutic PDC product candidate and is currently being evaluated in both Phase 2 and Phase 1 clinical studies. The FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma as well as orphan drug and rare pediatric disease designations for CLR 131 for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. In addition to the ongoing Phase 1 dose-escalation study and the Phase 2 (CLOVER-1) trial, the company recently initiated a Phase 1 open-label, dose-escalating study in pediatric solid tumors and lymphoma to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors.

On September 16, 2019 ImmunoPrecise Antibodies reported that it will participate in the 17th Annual Discovery on Target (DOT) being held Boston, MA September 16-19 (Press release, ImmunoPrecise Antibodies, SEP 16, 2019, View Source [SID1234539545]). With over 1,300 attendees and a variety of keynote speakers, training seminars, short courses, roundtables, and networking functions, DOT is said to be the industry’s preeminent event on novel drug target and technologies.

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Jennifer Bath, Ph.D., and Barry Duplantis, Ph.D., will be available at booth 308 to discuss with attendees how ImmunoPrecise Antibodies’ broad range of products and services, including our B cell Select antibody discovery platform, can streamline and accelerate their therapeutic antibody development efforts. Attendees can schedule a meeting with Jennifer or Barry by emailing Barry at [email protected] or by using the Brella networking app.

On September 16, 2019 Context Therapeutics, a clinical-stage biopharmaceutical company dedicated to advancing medicines for hormone driven cancers, reported a clinical collaboration with SOLTI, a leading collaborative and academic group in Spain dedicated to clinical and translational research in breast cancer (Press release, Context Therapeutics, SEP 16, 2019, View Source [SID1234539544]). This clinical collaboration, being supported by Context and sponsored by SOLTI, is a window of opportunity study (WOO) in the neoadjuvant setting for breast cancer.

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During the study, patients participating in the ONAWA (ONApristone Window Assessment) trial will receive oral doses of the progesterone receptor antagonist, Apristor (onapristone ER). Patients will be biopsied on day one, followed immediately by treatment and a final biopsy after three weeks, on the day of their full lumpectomy or mastectomy. Data generated from this study is intended to confirm the Recommended Phase 2 Dose (RP2D) of Apristor and to provide comprehensive biomarker data to further validate that the antitumor activity of Apristor is driven through downregulation of progesterone receptor and associated signaling pathways. This data will support Context’s ongoing and planned Phase 2 studies in breast, ovarian, and endometrial cancers.

"We are thrilled to enter into this collaboration with SOLTI and facilitate this window of opportunity study. We expect that this study will provide additional biomarker data to support our planned Phase 2 studies in progesterone receptor positive (PR+) female cancers," said Martin Lehr, CEO of Context Therapeutics.

The study, conducted within SOLTI’s network, has two Principal Investigators, both members of SOLTI Governing Board: Dr. Meritxell Bellet, Senior Consultant at Breast Cancer Unit at Vall d’Hebron University Hospital and Dr. Cristina Saura, Head of Breast Cancer Unit at Vall d’Hebron University Hospital. "The majority of breast cancer patients have an hormone-dependent disease. The hormones estrogen and progesterone drive breast cancer progression in those patients, but antiestrogens are the only antihormonal therapy available to clinicians. As such, antiestrogen resistance is now a major clinical challenge," said Dr. Bellet. "We believe that a progesterone receptor antagonist has the potential to address antiestrogen resistance and/or potentiate antiestrogen activity, which we believe will lead to better outcomes for patients. This window of opportunity provides us with the first clinical opportunity to delve deep into how progesterone receptor antagonists modulate the breast cancer tumor and its microenvironment."

About Hormone Driven Breast Cancer
Hormone receptor positive (HR+) breast cancer is the most common form of breast cancer and accounts for more than 70% of all breast cancers. HR+ cancer is usually treated with antiestrogen therapies first that help stop tumor growth. For many patients, antiestrogen therapy becomes ineffective over time and the cancer becomes resistant to antiestrogen therapy. In this recurrent setting, progesterone receptor has emerged as a prominent resistance mechanism. It is estimated that there are over 750,000 patients with recurrent disease worldwide.

About Window of Opportunity Trials
Window of opportunity (WoO) trials take advantage of natural scheduling delays that occur between initial consultation and surgery. This allows learning about anticancer activity of the intervention in a patient who has not been exposed to previous therapies. Such studies can better define biological effects of the therapy and outline the target patient population for the following studies. In turn, development and identification of promising drugs could speed up. WoO trials are usually short, in the order of 2–6 weeks of treatment, making it difficult to achieve clinical endpoints such as objective response. The endpoint of WoO trial is usually biomarker modulation. The collection of before and after treatment tumor biopsies allows determination of extent of target inhibition, cell proliferation and apoptosis, and identification of other biomarkers.

About Apristor
Apristor (onapristone extended release) is a potent and specific antagonist of the progesterone receptor that is orally administered. Currently, there are no approved therapies that selectively target PR+ cancers. Preliminary preclinical and clinical data suggest that Apristor has anticancer activity by inhibiting the binding of progesterone receptor to chromatin, downregulating cancer stem cell mobilization, and blocking immune evasion. Apristor is an investigational drug that has not been approved for marketing by any regulatory authority.

On September 16, 2019 Blue Earth Diagnostics, a Bracco company focused on molecular imaging diagnostics, reported results from an investigational clinical trial ("FALCON") evaluating the impact of 18F-fluciclovine PET/CT imaging on the clinical management of men with biochemically recurrent prostate cancer eligible for salvage therapy (Press release, Blue Earth Diagnostics, SEP 16, 2019, View Source [SID1234539543]). The FALCON trial is a UK-based, prospective, multi-center, open-label study (NCT02578940). Its primary endpoint examined the percentage of men who had their management plan changed after an 18F-fluciclovine PET/CT scan.

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Axumin (fluciclovine F 18) injection is approved for use in positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood levels of prostate specific antigen (PSA) following prior treatment. (For additional product information please see the end of this news release.)

Investigators in the FALCON trial recorded intended patient management plans prior to 18F-fluciclovine PET/CT imaging and then recorded how the plans were altered following review of the scan results. Results of the trial indicated that 64% (66/104) of patients had their clinical management plan changed when results of 18F-fluciclovine PET/CT imaging were added to the standard-of-care diagnostic work-up. Of those changes, 65% (43/66) were classified as "major," denoting a change in treatment modality (e.g. salvage radiotherapy to androgen deprivation therapy (ADT)).

Results from the study were summarized in an oral presentation, "Impact of positron emission tomography (PET) with 18F-fluciclovine PET/CT on management of patients with recurrence of prostate cancer: results from the FALCON trial," by David Bottomley, MBBS, St. James Institute of Oncology, Leeds UK, at the 2019 American Society for Radiology Oncology (ASTRO) Annual Meeting, September 15 – 18, 2019.

"We are very pleased to share results from the FALCON study with the radiation oncology community at ASTRO and look forward to publishing the results in an upcoming peer-reviewed journal," said Jonathan Allis, D. Phil., CEO of Blue Earth Diagnostics. "As part of our mission to develop and commercialize innovative PET imaging agents for cancer, Blue Earth Diagnostics conducted the FALCON and LOCATE studies to evaluate the utility of a 18F-fluciclovine PET/CT scan in providing physicians with actionable information for the management of men with recurrent prostate cancer. Each of these two independent, prospective studies arrived at similar conclusions – that 18F-fluciclovine PET/CT located recurrent disease in the majority of men in the study, which frequently resulted in major changes to their management plans for biochemical recurrence."

"The FALCON study evaluated men with biochemically recurrent prostate cancer who were being considered for curative-intent salvage therapy, and compared their treatment plans before and after 18F-fluciclovine PET/CT imaging to assess whether or not it impacted their management," said David Bottomley, MD, St. James Institute of Oncology, Leeds UK. "Results indicated that management plans were revised for the majority of patients, with 65% of revisions involving a major change in treatment modality. These results indicate that decisions based on 18F-fluciclovine PET/CT findings may facilitate more personalized management in men with biochemically recurrent prostate cancer. Investigation of the long-term clinical outcomes of these changes in management is warranted."

The primary endpoint of the FALCON trial examined the percentage of men who had their management plan changed following an 18F-fluciclovine scan. Previously planned therapeutic management was revised after an 18F-fluciclovine PET/CT scan in 64% (66/104) of patients. Of the patients with revised treatment plans, major revisions (e.g., salvage radiotherapy to hormone deprivation or watchful waiting) were made for 65% (43/66) of patients. Salvage treatment was revised to watchful waiting for 24% (16/66) patients and to systemic therapy for 24% (16/66) patients, and 17% (11/66) experienced alternative changes to their treatment modality. Of the patients with revised treatment plans, 35% (23/66) had their intended radiotherapy/brachytherapy plans modified. The safety profile of 18F-fluciclovine in the FALCON trial is consistent with that described in the approved U.S. Prescribing Information.

"Between 30 – 40% of patients with prostate cancer will develop local or distant recurrences within 10 years of radical prostatectomy or radiation therapy, underscoring the need for accurate information on the extent and location of recurrent disease," said Gerald L. Andriole, MD, the Robert K. Royce Distinguished Professor and Chief of Urologic Surgery at Washington University School of Medicine and lead author on behalf of the LOCATE study group. "Results of the FALCON study are consistent with those of the U.S., multi-center LOCATE study of 213 patients, which demonstrated that 59% of men with recurrent prostate cancer following prior treatment had a change in their management plan after 18F-fluciclovine PET/CT imaging."

About the FALCON Trial

The FALCON trial, "Fluciclovine (18F) PET/CT in biochemicAL reCurrence Of prostate caNcer (FALCON)," was an open-label, multi-center study in the UK designed to assess the clinical utility of 18F-fluciclovine PET imaging in the management of patients with prostate cancer with biochemical recurrence after initial treatment. The primary endpoint was to evaluate the clinical impact of 18F-fluciclovine in affecting treatment decisions and was assessed by comparing records of the patient’s treatment plan after an 18F-fluciclovine PET scan with the treatment plan prior to the scan. Secondary endpoints included evaluation of the optimal PSA threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine involvement and safety.

The FALCON trial was jointly funded by Innovate UK and Blue Earth Diagnostics and was conducted at six leading institutions in the UK: Oxford University Hospitals NHS Foundation Trust, University College London, Kings College London, The Royal Marsden NHS Foundation Trust, The Leeds Teaching Hospitals NHS Trust, Mount Vernon Cancer Centre and Greater Glasgow Health Board. Additional information about the FALCON trial is available at: www.clinicaltrials.gov (NCT02578940).

This press release is intended to provide information about Blue Earth Diagnostics’ business in the United States and Europe. Please be aware that the approval status and product label for Axumin varies by country worldwide. For EU Axumin product information refer to: View Source;mid=WC0b01ac058001d124.

U.S. INDICATION AND IMPORTANT SAFETY INFORMATION ABOUT AXUMIN
INDICATION
Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full Axumin prescribing information is available at www.axumin.com.

About Axumin (fluciclovine F 18)

Axumin (fluciclovine F 18) injection is a novel product indicated for use in positron emission tomography (PET) imaging to identify suspected sites of prostate cancer recurrence in men. Recurrence of prostate cancer is suspected by an increase in prostate specific antigen (PSA) levels following prior treatment. PET imaging with Axumin may identify the location and extent of such recurrence. Axumin was developed to enable visualization of the increased amino acid transport that occurs in many cancers, including prostate cancer. It consists of a synthetic amino acid that is preferentially taken up by prostate cancer cells compared with surrounding normal tissues and is labeled with the radioisotope F 18 for PET imaging. Fluciclovine F 18 was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences. Axumin was approved by the U.S. Food and Drug Administration in May 2016, following Priority Review, and is the first product commercialized by Blue Earth Diagnostics, which licensed the product from GE Healthcare. The molecule is being investigated by Blue Earth Diagnostics for other potential cancer indications including neuro-oncology.

On September 16, 2019 Precision BioSciences, Inc. (Nasdaq: DTIL), a genome editing company dedicated to improving life through the application of its pioneering, proprietary ARCUS platform, reported the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for PBCAR20A, the Company’s second off-the-shelf chimeric antigen receptor (CAR) T cell therapy program (Press release, Precision Biosciences, SEP 16, 2019, View Source [SID1234539541]). Wholly owned by Precision, PBCAR20A is an allogeneic anti-CD20 CAR T therapy candidate in development for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). The company plans to initiate a Phase 1/2a clinical trial in the fourth quarter of 2019, with initial data expected in 2020. The study will include patients with NHL, of which a subset will have the diagnosis of mantle cell lymphoma (MCL). Precision BioSciences has received Orphan Drug Designation for MCL and plans to pursue this indication.

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"FDA clearance to begin clinical trials with our anti-CD20 off-the-shelf CAR T therapy candidate is a significant milestone for Precision. Closely following the initiation earlier this year of our first clinical trial with the anti-CD19 allogeneic CAR T therapy candidate PBCAR0191, today’s announcement demonstrates our ability to advance multiple product candidates in parallel into the clinic, leveraging the unique capabilities of our ARCUS genome editing platform, CAR T development approach and a highly differentiated manufacturing process developed in house," commented Matt Kane, Chief Executive Officer and Co-Founder of Precision BioSciences. "I am delighted that our team continues to deliver ahead of expectations."

David Thomson, Chief Development Officer of Precision, said, "In preclinical disease models, PBCAR20A has demonstrated potent in vivo clearance of CD20+ tumor cells and overall tumor volume reduction. Furthermore, we did not observe any evidence of graft-versus-host disease in strict preclinical models. It is our hope that PBCAR20A will provide a new allogeneic CAR T therapy option with the benefits of reliable, off-the-shelf access and optimized cellular activity to patients living with NHL or CLL/SLL, where a significant need for new treatment options remains. Receiving orphan drug designation from the FDA for MCL means that we have a special opportunity to serve those patients previously treated for the MCL form of NHL, who have a poor prognosis with currently available treatments."

PBCAR20A will be Precision’s second off-the-shelf CAR T therapy candidate to enter the clinic, following PBCAR0191, an off-the-shelf anti-CD19 CAR T therapy candidate currently being evaluated in adult patients with relapsed or refractory (R/R) NHL or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL). Precision initiated dosing of subjects in a Phase 1/2a clinical trial of PBCAR0191 in April 2019, which continues to progress as planned; the company expects to present interim data from this trial at a scientific conference no later than the first quarter of 2020.

With the IND acceptance and expected upcoming clinical trial initiation for PBCAR20A, Precision’s clinical-stage portfolio of off-the-shelf CAR T therapy candidates for B-cell malignancies continues to grow. In the United States, B-cell malignancies account for 85 percent of all NHL cases, and CLL and SLL represent 25 to 30 percent of leukemias. While front-line treatments provide benefit to more than half of newly diagnosed NHL patients, at least a third of those who do benefit will become refractory, achieve only partial remission or relapse after remission. In addition, patients with CLL have seen limited success with autologous CAR T cell therapies, which is commonly ascribed to T cell exhaustion associated with this malignancy. Administration of healthy donor T cells via allogeneic CAR T cell therapy has the potential to overcome current challenges in CLL treatment, increase access to care in NHL and overcome treatment resistance due to CD19 loss. In addition, allogeneic CAR T therapy presents the possibility for combination treatment options by targeting both CD19 and CD20, which may help overcome resistance mechanisms in some patients.

Precision’s Off-The-Shelf CAR T Platform
Precision is advancing a pipeline of cell-phenotype optimized allogeneic CAR T therapies, leveraging fully scaled, proprietary manufacturing processes. The platform is designed to maximize the number of patients who can potentially benefit from CAR T therapy. Precision carefully selects high-quality T cells derived from healthy donors as starting material, then utilizes its unique ARCUS genome editing technology to modify the cells via a single-step engineering process. By inserting the CAR gene at the T cell receptor (TCR) locus, this process knocks in the CAR while knocking out the TCR, creating a consistent product that can be reliably and rapidly manufactured and is designed to prevent graft-versus-host disease. Precision optimizes its CAR T therapy candidates for immune cell expansion in the body by maintaining a high proportion of naïve and central memory CAR T cells throughout the manufacturing process and in the final product.

About the PBCAR20A Clinical Trial
PBCAR20A will be evaluated in a Phase 1/2a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation and dose-expansion clinical trial in adult NHL, CLL, and SLL patients. The trial will be conducted at multiple U.S. sites. For more information on the trial, visit www.clinicaltrials.gov, study identifier number NCT04030195.