On September 28, 2023 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported encouraging data from the single-arm pilot phase of the investigator-initiated CheMo4METPANC Phase 2 combination clinical trial evaluating the company’s CXCR4 inhibitor motixafortide, the PD-1 inhibitor cemiplimab, and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel alone, in first-line pancreatic cancer (PDAC) (Press release, BioLineRx, SEP 28, 2023, View Source [SID1234635498]).

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The data were published in an online abstract as part of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Pancreatic Cancer taking place in Boston, Massachusetts from September 27-30, 2023. An oral presentation of the data will take place later today, September 28, 2023.

The pilot phase of the Phase 2 study enrolled 11 patients with metastatic pancreatic cancer. As of May 2023, 6 patients (55%) experienced a partial response (PR) of which 4 (36%) were confirmed PRs with one patient experiencing resolution of the hepatic (liver) metastatic lesion. Three patients (27%) experienced stable disease, resulting in a disease control rate of 82%. These findings compare favorably to historic partial response and disease control rates of 23% and 48%, respectively, reported with the current standard of care, the chemotherapy combination gemcitabine and nab-paclitaxel.

"These initial data from the pilot phase of this ongoing Phase 2 study give us hope that motixafortide could potentially serve as the backbone of a new treatment regimen for PDAC, which is among the most difficult cancers to treat," said Philip Serlin, Chief Executive Officer of BioLineRx Ltd. "We are deeply committed to this important collaboration with Columbia University investigators and eagerly look forward to the data from the randomized phase of the trial."

Based on these pilot data, earlier this year, the CheMo4METPANC Phase 2 trial was amended to become a randomized study, with planned enrollment increasing from 30 to 102 patients. The trial, sponsored by Columbia University, is the first large, multi-center, randomized study evaluating motixafortide with a PD-1 inhibitor and first-line PDAC chemotherapies. A poster of the amended clinical trial design was presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held June 2-6 in Chicago, Illinois (see abstract).

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is expected to be the second leading cause of cancer-related death in the U.S. by 2023. Because it is typically diagnosed at later stages, greater than 80 percent of pancreatic cancer is inoperable. Most pancreatic cancer is incurable and unfortunately newer immunotherapy approaches, while beneficial against other solid tumor types, have had limited efficacy in pancreatic cancer due to immunosuppressive pathways.

An earlier single-arm, Phase 2a clinical trial (COMBAT/KEYNOTE-202) and pre-clinical studies evaluating motixafortide in combination with PD-1 immunotherapies and chemotherapies in PDAC have been promising, suggesting the ability of motixafortide to support an immune response.

Presentation at AACR (Free AACR Whitepaper) Special Conference in Cancer Research: Pancreatic Cancer

Westin Copley Place, Boston Massachusetts

Plenary Session Details

Title: CheMo4METPANC: Combination Chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) Motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) in METastatic treatment-naïve PANCreatic adenocarcinoma

Presenter: Gulam A. Manji, MD, PhD, Columbia University Irving Medical Center/New York Presbyterian, New York, N.Y.

Session: Plenary Session 3: Clinical Updates

Date: Thursday, September 28, 2023

Time: 2:30-4:40 pm EDT

About CheMo4METPANC Phase 2 Clinical Trial

The multi-center CheMo4METPANC Phase 2 clinical trial is a randomized, investigator-initiated clinical trial in first line metastatic pancreatic cancer. Sponsored by Columbia University, the study is evaluating the combination of CXCR4 inhibitor motixafortide, PD-1 inhibitor cemiplimab, and standard of care chemotherapies gemcitabine and nab-paclitaxel, versus gemcitabine and nab-paclitaxel, alone in 102 patients. The trial’s primary endpoint is progression free survival (PFS). Secondary objectives include safety, response rate, disease control rate, duration of clinical benefit and overall survival.

About Pancreatic Cancer

Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. In the United States in 2023, an estimated 64,000 adults will be diagnosed with the disease, which accounts for approximately 3% of all cancers in the U.S. and about 7% of all cancer deaths. Worldwide, an estimated 496,000 people were diagnosed with the disease in 2020. In the U.S., if the cancer is detected at an early stage when surgical removal of the tumor is possible, the 5-year relative survival rate is 44%. About 12% of people are initially diagnosed at this stage. If the cancer has spread to surrounding tissues or organs, the 5-year relative survival rate is 15%. For the 52% of patients who are initially diagnosed with metastatic cancer, the 5-year relative survival rate is 3%.[i] In particular, hepatic (liver) metastases are a critical risk factor driving poor prognoses for patients with metastatic PDAC. These data highlight the need for the development of new therapeutic options.

About Motixafortide in Cancer Immunotherapy

Motixafortide inhibits CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including pancreatic ductal adenocarcinoma (PDAC). Motixafortide leverages the expression of the CXCR4 receptor on different immune cells and potentiates the immune system against the tumor. Among CXCR4-expressing immune cells, some exhibit anti-tumoral activity, such as effector T cells and some exhibit pro-tumoral activity and support tumor growth. By blocking the CXCR4 receptor, motixafortide was shown in a Phase 2 study in pancreatic cancer patients to enhance anti-tumoral activity and to ameliorate the pro-tumoral activities by modulating the effector/suppressor cell ratio towards a proinflammatory profile.

On September 28, 2023 Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, reported the publication of positive results from a Phase I/II trial of its radiopharmaceutical 177Lu-satoreotide tetraxetan(satoreotide) in patients with previously treated, progressive neuroendocrine tumours (NETs), in the European Journal of Nuclear Medicine and Molecular Imaging (Press release, Ariceum Therapeutics, SEP 28, 2023, View Source [SID1234635497]).

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Satoreotide combines Ariceum’s proprietary peptide satoreotide – a first-in-class and best-in-class antagonist of the somatostatin receptor 2 (SSTR2) – with the radioactive isotope ‘payload’ 177Lutetium. SSTR2 is a cell surface protein often overexpressed in certain cancers, including NETs and small cell lung cancer (SCLC).

The Phase I/II trial was initiated by Ipsen, and recently completed after Ariceum acquired satoreotide from Ipsen. This international study was conducted in 7 countries – Australia, Austria, Canada, Denmark, France, Switzerland, and the UK – and enrolled 40 patients with advanced, SSTR2-positive NETs. The primary tumours of the patients included progressive, grade 1 and 2 (≈60%) gastroenteropancreatic (GEP), and (a)typical lung NETs, paraganglioma, and pheochromocytoma. All patients had undergone several lines of treatment, including chemo- and/or radiotherapy (45%), before they were treated with 177Lu-satoreotide. Most patients received three infusions of satoreotide, with the median cumulative radiation dose being 13.0 GBq.

Of the 38 patients for whom full results were obtained, 28 (73.7%) achieved stable disease, as determined eight weeks after the last infusion. A further 8 (21.1%) experienced a partial response (a reduction in tumour size) – giving a total Disease Control Rate (DCR) of 94.7%. 17 of the 40 patients (42.5%) experienced grade ≥3 treatment‑related adverse events, the most common being lymphopenia, thrombocytopenia, and neutropenia. Two patients developed myeloid neoplasms considered treatment-related by the investigator.

The authors of the study, titled "A phase I/II study of the safety and efficacy of [177Lu]Lu‑satoreotide tetraxetan in advanced somatostatin receptor‑positive neuroendocrine tumours", concluded satoreotide "has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs". They also discussed that the lower administered activity, 3 cycles of 4.5 GBq compared to 4 cycles of 7.4 GBq with 177Lu-DOTATATE, may offer advantages regarding the treatment burden for patients, but also in terms of reduction of nuclear waste and direct radioisotope costs. A 5-year follow-up study is ongoing.

Manfred Rüdiger, PhD, Chief Executive Officer of Ariceum Therapeutics, said: "These exciting new data demonstrate the great potential of our targeted radiopharmaceutical, satoreotide, for treating patients with advanced neuroendocrine tumours. Not only did a high proportion of treated patients achieve stable disease or better, but they did so on a lower dose of radiation than the investigators initially thought was needed. These results will greatly assist Ariceum in further developing satoreotide for hard-to-treat neuroendocrine cancers such as small cell lung cancer."

Further details on the study can be found on Clinical Trials, under identifier NCT05017662.

Citation:

Wild, D., Grønbæk, H., Navalkissoor, S. et al. A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours. Eur J Nucl Med Mol Imaging (2023). View Source

On September 28, 2023 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported that new data from the ongoing OPTIMIZE-1 Phase 2 study of the company’s lead asset mitazalimab, a best-in-class CD40 mAb agonist, will be presented in oral and poster presentations at the AACR (Free AACR Whitepaper) (American Association for Cancer Research) Special Conference on Pancreatic Cancer, being held in Boston September 27-30, 2023 (Press release, Alligator Bioscience, SEP 28, 2023, View Source [SID1234635496]). Preclinical mitazalimab data were also recently presented in a poster presentation at the International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) (CICON), held in Milan September 20-23, 2023.

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"The data reported in these three presentations add to the growing clinical evidence demonstrating that mitazalimab induces relevant activation of the immune system leading to enhanced anti-tumor responses to chemotherapy and provides durable benefits to patients with metastatic pancreatic cancer," said Søren Bregenholt, CEO of Alligator Bioscience. "We are very pleased to share these important developments at two of the year’s most important oncology conferences, which have allowed us to update the scientific community on the great clinical progress we are making with mitazalimab in the OPTIMIZE-1 study, ahead of the topline readout in early Q1 next year."
Oral presentation at AACR (Free AACR Whitepaper): "CD40 agonist mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Interim efficacy results of the OPTIMIZE phase 1b/2 study"

Date/Time: Thursday 28 September, 2023, 2.15 – 4.40 pm EDT
Session: Plenary Session 3: Clinical Updates
Presenter: Teresa Macarulla, Vall d’Hebrón University Hospital, Barcelona, Spain

Interim efficacy analysis of 57 evaluable patients from the OPTIMIZE-1 study (NCT04888312) that were announced in June 2023
Overall response rate per RECIST v1.1 was 43.9% (25 patients with partial response); an additional 19 patients achieved stable disease, resulting in a 77.2% disease control rate
Median time to response was 2.2 months and median duration of response was 8.7 months
Results demonstrated encouraging anti-tumor activity in mPDAC with good durability of responses, meriting continued development, possibly in a randomized setting
The OPTIMIZE-1 study continues to progress and remains on track for top-line readout in early Q1 2024.

Poster presentation at AACR (Free AACR Whitepaper): "Interim pharmacodynamic analyses of mitazalimab in combination with FOLFIRINOX in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) identify CD4 effector T cells as a correlate of treatment outcomes"

Date/Time: Friday 29 September, 2023, 4.40 – 6.40 pm EDT
Session: Poster Session C
Presenter: Dr. Gregory Beatty, Abramson Cancer Center & Division of Hematology-Oncology, University of Pennsylvania

Interim pharmacodynamic analyses and their association with outcomes from the OPTIMIZE-1 study, demonstrating that mitazalimab and mFOLFIRINOX induce distinct immune responses in pancreatic cancer patients
Analyses demonstrated that the desired activation of the immune system after mitazalimab exposure was achieved revalidating its mechanism of action
Analyses also demonstrated that increases in CD4 effector T cells correlate with treatment outcomes and suggest a mitazalimab-specific contribution to tumor responses in patients with metastatic pancreatic cancer
Poster presentation at CICON: "Efficacy and pharmacodynamic biomarkers of mitazalimab in combination with chemotherapy in preclinical mouse models"

Details of anti-tumor efficacy of mitazalimab and FOLFIRINOX in a preclinical tumor model and pharmacodynamic biomarkers in peripheral blood, induced at early time points after treatment
Preclinical data demonstrated that mitazalimab synergizes effectively with FOLFIRINOX, inducing long-term survival in a preclinical tumor model
The pharmacodynamic biomarkers identified in these preclinical data are in agreement with data from a Phase 1 dose escalation study of mitazalimab in patients with advanced solid stage tumors (NCT02829099)
Together, these preclinical tumor model data support mitazalimab’s mechanism of action as also observed in the ongoing OPTIMIZE-1 study

On September 27, 2023 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported that the US Food and Drug Administration (FDA) has transferred the Investigational New Drug (IND) Application for its allogeneic CD19 CAR T azer-cel from Precision Biosciences Inc. (NASDAQ GS: DTIL) to Imugene, following the exclusive worldwide license acquired in August (Press release, Imugene, SEP 28, 2023, View Source [SID1234635467]).

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Imugene MD & CEO, Ms Leslie Chong said, "We are actively progressing the ongoing multi-centre Phase 1b (ClinicalTrials.gov ID NCT03666000) study using the recommended Phase 2 regimen of azer-cel as we prepare for the start of a potential Phase 2 registrational study at the earliest opportunity, and we expect the Clinicaltrials.gov ID will be updated to reflect Imugene being the sponsor imminently."

On September 27, 2023 ImmuneOnco Biopharmaceuticals (Shanghai) Co., Ltd. (referred to as "ImmuneOnco""the company’, Hong Kong Stock Exchange stock code: 01541.HK) reported that the newly developed humanized IgG1 CD24 antibody, IMM47, successfully completed the first subject enrollment and dosing in the Australian phase I clinical trial (Press release, ImmuneOnco Biopharma, SEP 27, 2023, View Source [SID1234655692]). This is another milestone achievement in the company’s rapid development.

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CD24 is widely expressed in a variety of solid tumors, including breast cancer, non-small cell lung cancer, colorectal cancer, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and lymphoma, and is considered an important biomarker of poor prognosis in these cancers. And it appears to be great potential in clinical research.

With high specificity and high affinity binding to CD24 expressed on tumor cells, IMM47 can block immunosuppressive signals transmitted from the CD24/Siglec-10 pathway to macrophages, natural killer cells (NK) and T cells. With genetically engineered improved IgG1 Fc, IMM47can also effectively activates macrophage and natural killer cell immune responses through powerful ADCP and ADCC. In preclinical animal in vivo efficacy studies, IMM47 was shown to significantly increase the number of M1 macrophages in tumor tissues and downregulate CD24 expression in tumor cells, either alone or in combination with PD-1/PD-L1 immune checkpoint inhibitors and other drugs. Both combinations have shown encouraging abilities to inhibit tumor growth.

In addition, the IND application for IMM47 to treat solid tumors has been accepted by the National Medical Products Administration (NMPA), and we also plan to submit an application to the U.S. Food and Drug Administration (FDA) in the near future. IMM47 has obtained an authorized patent in China, an approved patent application in Japan, a pending patent application in the United States and the European Union, and a pending PCT patent that may enter multiple signatory countries in the future.

The preclinical research results of the IMM47 have been published in "Antibody Therapeutics" on September 9, 2023, in tittle of "IMM47, a humanized monoclonal antibody that targets CD24, exhibits exceptional anti-tumor efficacy by blocking the CD24/Siglec-10 interaction and can be used as monotherapy or in combination with anti-PD1 antibodies for cancer immunotherapy"

Founder and Chairman of ImmunOnco, Dr. Tian, Wenzhi said: "I am very pleased to see that our Australian phase I clinical trial of IMM47 has successfully completed the first subject enrollment and dosing. This also marks that IMM47 has officially entered the clinical research stage. IMM47 is a humanized monoclonal antibodies targeting CD24 for cancer treatment. The antibody screening for CD24 was quite challenge due to its small size of extracellular domain which exhibits weaker immunogenicity. We persevered through the accumulation of a lot of trivial work and finally got the IMM47 molecule with high affinity and specificity. With differentiated molecular design, IMM47 can specifically bind to CD24 and effectively activate macrophages and natural killer cell immune responses. Preclinical studies have shown that IMM47 has strong anti-tumor activity with great clinical development value. We will quickly advance the clinical trial of IMM47 to benefit more patients."

Chief Medical Officer/Senior Vice President of ImmuneOnco Dr. Lu, Qiying said: "the successful completion of the first subject in the Australian Phase I clinical trial of IMM47 is of great significance for the company, marking that IMM47 officially entered the clinical research. After half year of unremitting efforts by the clinical team, ImmunOnco launched clinical trials in Australia, the first drug candidate for this target to achieve FPI globally. This is due to our first overseas deployment, thus accelerating the clinical verification of IMM47. In addition, we believe that the Australian trial will obtain valuable diverse ethnic clinical data. It will strengthen our ability to pursue collaborating opportunities with global pharmaceutical companies. We highly expect IMM47 drugable and look forward to bringing good news to cancer patients."