On September 5, 2022 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that an abstract with clinical trial results of its innate cell engager (ICE) AFM24 has been accepted for a poster presentation at the Congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) from 9-13 September 2022 in Paris (Press release, Affimed, SEP 5, 2022, View Source [SID1234618970]). The abstract includes phase 1 data on the safety, immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) from patients with locally advanced or metastatic, treatment refractory EGFR-positive solid tumors treated with AFM24 monotherapy.

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"These results represent a major milestone for our broad development program further assessing the efficacy of AFM24 as monotherapy and in combinations," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed. "AFM24 has now demonstrated the ability to activate both innate and adaptive immune cells, which may help to potentially overcome resistance to current therapies."

Additional Details about the Study and Poster Presentation
In the study, AFM24 was administered in doses up to 720 mg intravenously once weekly until disease progression, intolerable toxicity, patient withdrawal, or termination at the investigator’s discretion. Tumor types included mainly colorectal and non-small cell lung cancer.

AFM24-related treatment-emergent adverse events included infusion-related reactions, nausea and acneiform dermatitis. There were no on-study deaths. The maximum tolerated dose was not reached. As of March 2022, stable disease (SD) was observed in 10/27 evaluable patients out of which 4 remained in SD for more than 4 months.

Comprehensive PD studies of cytokines and immune cells in peripheral blood and tumor biopsies indicated the activation of the innate as well as the adaptive immune system starting at 160 mg. These findings supported the selection of 480 mg as the RP2D. Enrollment into three disease-specific cohorts is ongoing at this dose.

In addition, two combination studies with atezolizumab (AFM24-102) and the autologous NK cell product SNK01 (AFM24-103) are being conducted each with three disease-specific cohorts. The combination studies started at 160mg and are planned to be escalated to 480 mg.

Poster title: A Phase 1/2a Dose Escalation Study of AFM24 in Patients with Epidermal Growth Factor Receptor-expressing (EGFR) Solid Tumors: Results from Phase 1

Poster number: 754P

More details about the ESMO (Free ESMO Whitepaper) congress are available online at ESMO (Free ESMO Whitepaper) Congress 2022.

About AFM24
AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Affimed is evaluating AFM24 as a monotherapy (AFM24-101) for patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies.

The first-in-human phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation and expansion study can be found at www.clinicaltrials.gov using the identifier NCT04259450. Furthermore, AFM24 is evaluated in a phase 1/2a study in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab (AFM24-102, NCT05109442). Affimed and NKGen Biotech have initiated a phase 1/2a study, investigating AFM24 in combination with SNK01, NKGen Biotech’s NK cell product (AFM24-103, NCT05099549).

On September 5, 2022 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that the US-based diagnostic 64Cu SAR-Bombesin trial (SABRE NCT05407311)1 for patients with PSMA-negative prostate cancer is open for recruitment (Press release, Clarity Pharmaceuticals, SEP 5, 2022, View Source [SID1234618968]).

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SABRE (Copper-64 SAR-BisPSMA in Biochemical Recurrence of prostate cancer) is a Phase II Positron Emission Tomography (PET) imaging trial of participants with PSMA-negative biochemical recurrence (BCR) of prostate cancer following definitive therapy. It is a multi-centre, single arm, non-randomised, open-label trial of 64Cu-labelled SAR-Bombesin in 50 participants. The primary objectives of the trial are to investigate safety and tolerability of the product as well as its ability to correctly detect recurrence of prostate cancer.

Dr Andrei Iagaru, Lead Principal Investigator in the SABRE trial, commented, "We are very excited to initiate patient accrual for the SABRE trial which will explore and validate the clinical benefits associated with the novel SAR-Bombesin agent. We have been investigating Bombesin for many years and believe it is an agent with high diagnostic and therapeutic potential. We hope this trial will inform us on the role of SAR-Bombesin in diagnosing disease in PSMA-negative prostate cancer patients by imaging patients on day of injection and at ~24 hours after injection, with the delayed imaging being a novel feature enabled by 64Cu. In addition to investigating the clinical benefits of the product, we also look forward to leveraging centralised manufacture and on-demand delivery advantages of copper-based products. These features have potential to facilitate universal access to SAR-Bombesin and enhance accessibility to treatment facilities throughout the US.

"We look forward to expanding the trial sites and generating data for this next-generation product which could ensure both ease of access and improved treatment outcomes for BCR prostate cancer patients," said Dr Iagaru.

The SABRE trial was developed in response to strong demand from clinicians with prostate cancer patients whose cancer was not visible with currently approved PSMA diagnostic agents or conventional imaging (such as CT or MRI). It builds on the data generated in PSMA-negative prostate cancer patients at St Vincent’s Hospital imaged under the Therapeutic Goods Administration (TGA) Special Access Scheme (SAS).2 This data has demonstrated diagnostic imaging potential in PSMA-negative prostate cancer and highlighted potential utility of the product as a theranostic agent. SABRE also builds on a pilot diagnostic trial of SAR-Bombesin in breast cancer patients, the C-BOBCAT trial, which was recently presented at the prestigious American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting.3

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are excited to commence recruitment into the SABRE trial, having only received our Study May Proceed letter from the US Food and Drug Administration (FDA) in June. SABRE reinforces our commitment to running Clarity’s clinical trials for first approvals in the US under clinical protocols which have been reviewed by the US FDA. Subject to the outcomes of this Phase II trial, we will look to progress this diagnostic product into Phase III trials in the US as soon as possible.

"Given the promising data to date, indicating potential diagnostic and therapeutic benefits of SAR-Bombesin, we are committed to continuing generating data on the product with the SABRE trial following in quick succession from the BOP investigator-initiated trial in PSMA-negative prostate cancer participants that commenced at St Vincent’s Hospital in Sydney earlier this month. In parallel, we are also preparing a submission to the US FDA for an Investigational New Drug (IND) application for a therapeutic clinical trial with the product later this year.

"We look forward to recruiting and imaging participants in the SABRE trial and gathering further evidence of clinical, environmental and logistical benefits of SAR-Bombesin, hoping that it will provide a large patient population with accurate and precise detection and treatment of PSMA-negative prostate cancer," said Dr Taylor.

Clarity’s Prostate Cancer clinical trial program overview

About SAR-Bombesin
SAR-Bombesin is a highly targeted pan-cancer radiopharmaceutical with broad cancer application. It targets the gastrin-releasing peptide receptor (GRPr) present on cells of a range of cancers, including but not limited to prostate, breast and ovarian cancers. GRPr is found in approximately 75-100% of prostate cancers, including prostate cancers that don’t express PSMA (PSMA-negative)4-8. The product utilises Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-Bombesin is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu for therapy).

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide9. The National Cancer Institute estimates in 2022 there will be 268,490 new cases of prostate cancer in the US and around 34,500 deaths from the disease10.

Approximately 20% of prostate cancers with BCR are PSMA-PET negative11-14. These patients are therefore unlikely to respond to therapeutic PSMA-targeted products and currently have few treatment options available to them. Given the prostate cancer indication is one of the largest in oncology, there is a significant unmet medical need in this segment.

On September 4, 2022 POINT Biopharma Global Inc. (NASDAQ: PNT) (the "Company" or "POINT"), a company accelerating the discovery, development, and global access to life-changing radiopharmaceuticals, reported data will be released at ESMO (Free ESMO Whitepaper) Congress 2022 in Paris, France about the efficacy and safety of PNT2002 in the lead-in cohort of the SPLASH trial (Press release, Point Biopharma, SEP 4, 2022, View Source [SID1234618993]). An abstract is now available on the ESMO (Free ESMO Whitepaper) congress website at View Source, and an e-poster which contains updated data will be published and presented on Sunday, September 11th.

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The poster is titled "Efficacy and Safety of 177Lu-PNT2002 Prostate-Specific Membrane Antigen (PSMA) Therapy in Metastatic Castration Resistant Prostate Cancer (mCRPC): Initial Results from SPLASH" (e-Poster #1400P), and is scheduled for presentation on Sunday, September 11 from 9:00-17:00 CEST (Paris) by Dr. Aaron R. Hansen, staff medical oncologist of Princess Alexandra Hospital and an Associate Professor of Medicine at the University of Toronto.

In advance of the publication of the abstract, the Company recently hosted a 45-minute educational webinar entitled "Understanding the PNT2002 SPLASH Trial Control Arm". A replay of the webinar is available online at View Source

About the SPLASH Trial

The phase 3 SPLASH trial is a multi-center, randomized, open label assessment of PNT2002 in participants with PSMA-expressing mCRPC who have progressed on androgen receptor pathway inhibitor (ARPI) therapy and refuse, or are not eligible for, chemotherapy. The randomization phase of the study is expected to enroll approximately 400 participants across North America, Europe, and the United Kingdom. Participants will be randomized 2:1 with participants in arm A receiving PNT2002 and participants in arm B receiving either abiraterone or enzalutamide. Participants in arm B who experience centrally assessed radiographic progression and meet protocol eligibility will have the option to crossover and receive PNT2002. Patients will be subject to follow-up for up to 5 years from their first PNT2002 dose. The primary endpoint of the study is radiographic progression-free survival. Key secondary endpoints include overall response rate, overall survival, and pharmacokinetics.‍

On September 4, 2022 Ibex Medical Analytics, the leader in AI-powered cancer diagnostics, reported the launch and roll-out of Galen 3.0, a transformative solution offering new detection capabilities and a broad set of features to support pathologists in the diagnosis of multiple tissue types across various digital pathology workflows (Press release, Ibex Medical Analytics, SEP 4, 2022, View Source [SID1234618976]). Galen 3.0 is CE-Marked, approved in additional countries and now generally available to Ibex customers.

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Creating a new modality for cancer diagnosis, Galen is the first and most widely deployed AI technology in pathology and used in routine clinical practice at laboratories, hospitals, and health systems worldwide. Galen supports pathologists across numerous diagnostic tasks during the review of breast, prostate, and gastric biopsies and helps improve the quality of cancer diagnosis, reduce turnaround time, boost productivity and improve user experience for pathologists. Galen demonstrated outstanding outcomes across clinical studies performed in multiple pathology labs and diagnostic workflows1,2,3,4,5.

Galen 3.0 incorporates the very latest evolution of Ibex’s AI algorithms for detecting cancer and other clinically relevant features in prostate, breast, and gastric biopsies. To ensure very high accuracy and generalizability, Ibex trained the Deep Learning networks on huge, enriched data sets from laboratories worldwide that were digitized by multiple scanning systems, including rare prostatic malignancies such as intraductal carcinoma, neuroendocrine tumor, colorectal adenocarcinoma, lymphoma, and urothelial carcinoma. Galen also calculates a Gleason score, tumor size and percentage for each cancer slide, potentially enabling pathologists to save review time and reduce subjectivity.

"With an estimated 1.9 million new cancer cases diagnosed in the United States alone this year, we are excited to bring Galen 3.0 to pathology labs worldwide, providing clinically validated, automated decision-support tools that help pathologists diagnose cancer more rapidly and more accurately to support the high demand," said Issar Yazbin, Vice President of Product Management at Ibex. "Keeping our customers’ needs central to our research and development, we are proud to deploy Galen 3.0, bringing enhanced detection capabilities, improved user experience, increased interoperability tools and ease of implementation into existing clinical workflows."

Galen 3.0 features an open API (Application Programming Interface) accelerating interoperability and seamless integration with image management solutions, lab information systems and digital pathology workflow solutions. The Ibex API is already used in multiple collaborations between Ibex and leading digital pathology partners where Ibex’s AI findings are seamlessly integrated to the partners’ solutions. Version 3.0 also includes new customizable reporting modules, enabling every customer site to tailor the slide and case reports according to their own needs.

Ibex Medical Analytics presents at the European Congress of Pathology which takes place in Basel, Switzerland, between September 3-7 (booth no. 1).

On September 4, 2022 Leap Therapeutics, Inc. (NASDAQ: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the Company will be presenting data in first-line patients with advanced gastroesophageal adenocarcinoma (GEA) from the DisTinGuish study, a Phase 2a clinical trial evaluating Leap’s anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with tislelizumab, BeiGene’s anti-PD-1 antibody, and chemotherapy, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 being held on September 9-12 (Press release, Leap Therapeutics, SEP 4, 2022, View Source [SID1234618975]). Safety and early efficacy data will be presented from the WAKING study, a multicenter Phase 2 non-randomized trial evaluating DKN-01 plus Tecentriq (atezolizumab), Roche’s anti-PD-L1 antibody, in patients with advanced oesophagogastric adenocarcinoma (OGA).

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"Data from the DisTinGuish study continue to demonstrate promising results with the combination of DKN-01 plus tislelizumab and standard chemotherapy as a first-line treatment in patients with advanced gastroesophageal adenocarcinomas," said Samuel Klempner, MD, Associate Professor at Harvard Medical School. "The mature median progression-free survival of 11.3 months compares favorably with recent benchmarks in this patient group. The outcomes in the aggressive DKK1-high and the less checkpoint-inhibitor sensitive PD-L1-low (CPS < 5) subgroups are notable and encouraging. As the last patient enrolled in early April 2021, the overall survival results are also on track to show an increase over current standards. Gastroesophageal cancer patients and physicians want new biomarker-directed therapies to improve the standard of care in first-line treatment, and we are enthusiastic about the upcoming randomized clinical trial involving this encouraging DKN-01 combination."

"Early results from the WAKING study show the promise of boosting anti-tumor activity by targeting the Wnt signaling pathway and DKK1-driven tumor microenvironment modulation with a DKN-01 plus atezolizumab combination therapy strategy in patients with advanced OGA," said Fiona Turkes, MD, Clinical Research Fellow at The Royal Marsden Hospital. "We look forward to continuing to enroll patients and studying the biological mechanisms of this unique chemotherapy-free combination therapy, especially in those patients whose tumors express high levels of DKK1."

Key Findings DisTinGuish
DKN-01 and tislelizumab plus CAPOX was well tolerated in first-line treatment for advanced GEA patients, with a safety profile consistent with previous reports
Overall median progression-free-survival (PFS) of 11.3 months exceeds benchmark results in unselected patients and in all four important biomarker-directed subgroups
11.3 months PFS in DKK1-high and 12.0 months in DKK1-low
10.7 months PFS in PD-L1-low (CPS < 5) and 11.6 months in PD-L1-high (CPS > 5)
Median overall survival (OS) is not mature with only 44% of patients deceased as of the data cut (June 30, 2022), with a median duration on study of 15.7 months and last patient enrolled in early April 2021
High and durable overall response rate (ORR) in unselected and aggressive subgroups (DKK1-high and PD-L1-low) (mITT): 68% (1 CR, 14 PR) overall
DKK1-high: 90% ORR (9 PR)
DKK1-low: 56% ORR (1 CR; 4 PR)
PD-L1-low expression: 79% (11 PR)
100% (6/6) ORR in DKK1-high, PD-L1-low patients
PD-L1-high expression: 67% (1 CR; 3 PR)
75% (3/4) ORR in DKK1-high, PD-L1-high patients
Key Findings WAKING
DKN-01 up to 600mg every 2 weeks in combination with atezolizumab was considered safe
3 patients with the longest time on treatment received the 600mg dose level
At time of data cut off (August 16, 2022), 18 patients were enrolled in the study
12 patients were treated in initial phase
10 patients were response evaluable at the time of data cut-off
1 patient had a PR and DKK1 expression of 81% tumor percentage score (TPS)
Disease control rate: 50% (1 PR, 4 SD, 5 PD)
Elevated baseline DKK1 expression (TPS > 20%) may be associated with clinical response
4 DKK1-high patients: Best ORR 25% (1 PR, 1 SD, 1 PD, 1 NE)
Translational analyses and assessment of PD-L1 status are ongoing
Safety
No dose-limiting toxicity (DLT) was observed, and no formal maximum tolerated dose (MTD) was reached
No treatment-related deaths occurred, and no dose reductions were required
Leap Poster Details:
Title: DKN-01 and Tislelizumab + Chemotherapy as First-line (1L) Investigational Therapy in Advanced Gastroesophageal Adenocarcinoma (GEA): DisTinGuish Trial
First Author: Samuel J. Klempner, Harvard Medical School
Session Category: Poster Session
Session title: Oesophagogastric cancer
Date and time: Monday, September 12, 2022, at 12:00 CET
Poster Number: 1213

Title: Safety and efficacy of Wnt inhibition with a DKK1 inhibitor, DKN-01, in combination with atezolizumab in patients with advanced oesophagogastric adenocarcinoma (OGA): Phase IIa results of the WAKING trial
First Author: Fiona Turkes, The Royal Marsden NHS Foundation Trust
Session Category: Poster Session
Session title: Oesophagogastric cancer
Date and time: Monday, September 12, 2022, at 12:00 CET
Poster Number: 1253

About the DisTinGuish Study
The DisTinGuish study (NCT04363801) is a Phase 2a study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, with or without chemotherapy as first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being conducted in two parts in the United States and the Republic of Korea. Enrollment of Part A has been completed with 25 first-line HER2- G/GEJ cancer patients whose tumors express either high levels of DKK1 (DKK1-high) or low levels of DKK1 (DKK1-low). Part B of the study has completed enrollment patients with second-line DKK1-high G/GEJ cancer. Part C of the study will be a randomized controlled trial of DKN-01 in combination with tislelizumab and chemotherapy compared to tislelizumab and chemotherapy. Leap is conducting this combination study as part of an exclusive option and license agreement with BeiGene.

About the WAKING Study
The WAKING study (NCT04166721) is a Phase IIa/b nonrandomized, open-label, multicenter study to be conducted concurrently in 2 Parts. Approximately 52 patients aged 18 years or older with inoperable, histologically confirmed locally advanced or metastatic G/GEJ adenocarcinoma with measurable disease (RECIST v1.1) requiring therapy will be enrolled in the study. Both parts are designed to evaluate safety, tolerability, and efficacy of the combination therapy of DKN-01 and atezolizumab in immunotherapy naïve, PD-L1 unselected G/GEJ adenocarcinoma patients. Treatment continues in repeating 14-day cycles until patient meets criteria for discontinuation or is no longer deriving clinical benefit. The WAKING study is being led by the Royal Marsden Hospital in the United Kingdom with financial support from Roche.