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HighField Biopharmaceuticals Announces Positive Phase 1a Data of HF1K16, a new Immuno-Oncology Drug, For Patients with Recurrent and Refractory Glioma

On October 23, 2023 HighField Biopharmaceuticals, a clinical stage immuno-oncology company using lipid-based therapeutics to treat cancer, reported results of its Phase 1a study of HF1K16 showing three of five patients with recurrent and refractory glioma had maintained disease control for more than 8 months with one patient experiencing complete response (Press release, HighField Biopharmaceuticals, OCT 23, 2023, View Source [SID1234636287]). HF1K16 is a drug encapsulated immune modulating liposome containing all-trans retinoic acid.

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"These encouraging results show HF1K16 is well tolerated and patients have experienced significant disease control," said Yuhong Xu, CEO of HighField. "We are currently enrolling additional glioma patients in our Phase 1b/2 extension trial to confirm these outcomes and expect to have the results in the first quarter of 2024."

Dr. Xu and HighField Chief Business Officer Donald Wyatt will attend BIO-Europe November 6 – 8, 2023, in Munich, Germany, to discuss the company’s unique lipid-based drug, including details of the Phase 1a trial. Dr. Xu and Mr. Wyatt can be contacted through the conference’s online Partnering platform.

Of the three patients who had experienced disease control, one patient achieved complete remission after 12 months of treatment and has been cancer free afterwards for 7 months. One of the other two patients, with grade IV glioblastoma, maintained stable disease for more than 4 months. The third patient had stable disease for nearly 3 months and survival to date for more than 9 months. HF1K16 was well tolerated with no high grade adverse effects at all dose levels.

HF1K16 is a unique liposome construct of ATRA, a small molecule metabolite of vitamin A. It is administered by infusion, travels through the blood stream and infiltrates the tumor microenvironment. ATRA is released and initiates the maturation of myeloid-derived suppressor cells (MDSCs).

MDSCs are immature myeloid cells which have not differentiated. ATRA promotes the maturation and differentiation of MDSCs into functional cells, such as dendritic cells, which then summon T cells to attack the cancer.

The Phase 1b/2 trial, underway in China, and will assess safety and efficacy as well as evaluate changes in MDSC numbers and phenotypes. See NCT05388487 at clinicaltrials.gov.

ImmuneOncia Announces Phase 1 Results of CD47 Antibody at ESMO 2023

On October 23, 2023 ImmuneOncia (CEO Heung Tae Kim) reported the results of its Phase 1a solid tumour clinical trial (IMC-002-K102 Study) of IMC-002, a CD47 monoclonal antibody, at the European Society for Medical Oncology (ESMO 2023) held in Madrid, Spain on October 23rd, 2023 (Press release, ImmuneOncia Therapeutics, OCT 23, 2023, View Source [SID1234636286]).

The dose-escalation study aimed to assess the safety and tolerability, and to establish the recommended Phase 2 dose (RP2D) of IMC-002. From May 2022 to October 2023, a total of 12 patients were enrolled in four dose cohorts, each receiving IMC-002 at doses of 5, 10, 20, or 30 mg/kg every 2 weeks (Q2W).

The clinical data showed no dose-limiting toxicities (DLT). 92% of treatment-related adverse events (TRAE) were of Grade 1-2, with 94% occurring during the first treatment cycle. Common side effects associated with anti-CD47 therapy, such as infusion-related reactions, thrombocytopenia, and neutropenia, were not reported.

The recommended Phase 2 dose of 20 mg/kg every 3 weeks (Q3W) was established. 6 out of 11 evaluable patients with measurable lesions also demonstrated stable disease (SD). 5 of the patients had liver cancer, and 1 had breast cancer.

Professor Ho Young Lim of Samsung Medical Center, the Principal Investigator (PI) of IMC-002, commented, "CD47 is a promising immune checkpoint inhibitor for activating the anticancer function of macrophages, but it is also expressed on normal cells, raising concerns about hemolytic anemia and thrombocytopenia. However, most of the side effects of IMC-002 were mild, and 4 out of 6 SD patients received long-term treatment for over 6 months. This clinical trial has confirmed the safety of IMC-002."

Heung Tae Kim, CEO of ImmuneOncia, said, "The recommended dose of every 3 weeks (Q3W) enhances patient convenience and opens up combination treatment opportunities with immune checkpoint inhibitors such as PD-(L)1 or other cytotoxic agents. Observing disease control for over 6 months in 4 SD patients, we expect to further confirm efficacy in Phase 1b, which is set to commence in November this year. We hope to further advance towards our goal of providing patients with a best-in-class anti-CD47 therapy."

IMC-002 is an anti-CD47 antibody that functions as an immune checkpoint inhibitor against macrophages, allowing them to attack cancer cells by blocking the ‘don’t eat me’ signal between CD47 on cancer cells and SIRPα on macrophages. IMC-002 is expected to have a good safety profile by minimising binding to normal cells, including red blood cells.

ImmuneOncia is a biotechnology company specialising in immuno-oncology drug development. In addition to the CD47 antibody IMC-002, ImmuneOncia also has a wide range of pipeline that includes the Phase 2 clinical-stage PD-L1 antibody IMC-001, and the preclinical-stage bispecific antibody IMC-201.

5-Year Head & Neck Cancer Survival Increased From 45% to 73% in CEL-SCI’s Target Population, Cutting Risk of Death in Half, as Presented at Leading Cancer Conference ESMO 2023

On October 23, 2023 CEL-SCI Corporation (NYSE American: CVM) reported that it has finalized the selection criteria for the head and neck cancer target population to be treated with the Company’s immunotherapy drug Multikine (Leukocyte Interleukin, Injection) (Press release, Cel-Sci, OCT 23, 2023, View Source [SID1234636285]). Five-year survival in the target population was 73% alive for Multikine-treated patients vs only 45% alive in the control who did not receive Multikine, with the five-year risk of death cut in half for Multikine-treated subjects in the target population versus the control. These data, which are statistically significant and accompanied by strong hazard ratios, are a crucial achievement on the path for the approval of Multikine. CEL-SCI presented the data for the first time at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Spain on October 22, 2023. The selection criteria for this target population were developed based on the completed Phase 3 randomized controlled trial, advice from regulators, and advice from physician consultants associated with the University of California San Diego Cancer Center and Yale Medical School, recognized as among the nation’s most esteemed immuno-oncologists in head and neck cancer.

Patients within this Multikine target population can be readily identified upon diagnosis with tests that physicians routinely use in cancer screening—another crucial achievement towards making Multikine available for use, as it is given immediately after diagnosis and before any other treatment. Working with regulators, CEL-SCI can now write an appropriate approval label defining Multikine’s target population, which is supported by strong positive data from the Phase 3 trial. The target population is estimated to cover ~145,000 advanced primary head and neck cancer patients globally per year.

The final Multikine selection criteria are:

No involvement of disease in the lymph nodes ("N0") and no extracapsular spread of the tumor, as confirmed using PET-CT/MRI imaging, and
Low PD-L1 tumor expression (defined as tumor proportion score < 10).
CEL-SCI’s ESMO (Free ESMO Whitepaper) poster reports three major new advancements supporting Multikine’s approvability:

First, Multikine is most effective in patients having tumors with low PD-L1 expression, consisting of about 70% of the study population. (It should be noted that immune checkpoint inhibitors like Keytruda and Opdivo appear to work best in patients with tumors having high PD-L1 expression).
Second, the Multikine target population can now be readily identified upon diagnosis, prior to surgery, using tests that physicians routinely use in cancer screenings.
Third, Multikine patients in the target population saw a significant increase in 5-year overall survival, from 45% for control patients who did not receive Multikine to 73% for Multikine-treated patients, shown in graph 1 above.
A 28% 5-year absolute survival advantage (73% vs 45%, p=0.0015), hazard ratio 0.35 (95% CIs [0.18, 0.66], Wald p=0.0012). The p-value of 0.0015 makes these results strongly significant as a statistical matter. The hazard ratio for Multikine vs control was 0.35, meaning that the Multikine-treated patients had, on average, about 65% lower risk of death at any given time. CEL-SCI is not aware of any head and neck cancer therapy that has shown such a large 5-year survival benefit. In addition, the hazard ratio’s "95% confidence interval" upper bound was 0.66, which supports CEL-SCI’s confidence that a confirmatory trial of Multikine in the target population would likely be a success. These results and statistics support CEL-SCI’s confidence that the data should be sufficient for requesting immediate approval for Multikine to treat these patients who currently have an unmet need for better outcomes.

Another finding presented at ESMO (Free ESMO Whitepaper) is also very important because it predicts improved survival. This finding refers to pre-surgery disease downstaging, which is when the physician assesses a lower stage of disease after Multikine therapy compared to before Multikine therapy. Graph 2 above clearly indicates that Multikine-treated patients with downstaging (improved disease, the green top line) have much better survival. This data is strongly significant as a statistical matter, with a p-value below 0.0002.

Geert Kersten, Chief Executive Officer of CEL-SCI, said: "We are now able to identify upon diagnosis which patients are most likely to have pre-surgery responses to Multikine and improved survival, as seen in the new ESMO (Free ESMO Whitepaper) data. This is a new sign of hope for head and neck cancer patients and a critical milestone for Multikine towards achieving regulatory approval. Because Multikine is a neoadjuvant (pre-surgical) immunotherapy, identifying patients who benefit from Multikine upon diagnosis was very difficult, and we welcomed the assistance of regulators and expert physician consultants to help us. With this success announced at ESMO (Free ESMO Whitepaper), we are eager to present these new data to regulators."

John Cipriano, Senior VP of Regulatory Affairs at CEL-SCI, said: "Patients with this disease have a clear unmet medical need for better outcomes. Multikine’s demonstrated effects in the new intended target population are overwhelmingly large and strong as a statistical matter and support the observed Multikine efficacy. While Multikine has not yet been tested prospectively in the new target population, the Phase 3 data present a compelling case for immediate patient access to Multikine because the Phase 3 study results showed prospectively that Multikine led to pre-surgical responses which in turn led to longer life. Regulators understand that patients should not have to wait before gaining access to these benefits, particularly given Multikine’s safety profile and data that mechanistically and empirically supports the target population definition. There are specific pathways in Europe, the UK, Canada, and the U.S. for such approvals, and we are currently working towards this goal. We filed requests with the UK and European regulatory bodies within the past month, and we intend to press forward with these new results in Canada and the U.S. in the coming months. Therefore, we hope to receive approval in the target population without having to wait for completion of a confirmatory study."

CEL-SCI’s Chief Scientific Officer, Eyal Talor, Ph.D., a co-author of CEL-SCI’s ESMO (Free ESMO Whitepaper) presentation, provided more detail on the data. "This year’s ESMO (Free ESMO Whitepaper) data presentation also relates to pre-surgery disease downstaging, which occurs, for example, when the disease stage goes down from Stage IV to Stage III during Multikine treatment before surgery. In the overall Phase 3 study population, we saw that patients with disease downstaging survived longer than those without. Therefore, we concluded that Multikine benefited patients who had downstaging before surgery. The target population selection criteria are designed to capture as many responder patients as possible, and indeed we saw a 35% rate of pre-surgical downstaging in the Phase 3 study subjects who met these selection criteria when treated with Multikine. This high rate of downstaging and tumor responses from Multikine led to the increase in overall survival seen in the target population and this is why the risk of death was cut in half for Multikine-treated patients as compared to control."

Click here for a link to CEL-SCI’s ESMO (Free ESMO Whitepaper) 2023 poster presentation entitled: "Tumor Node stage shift following Leukocyte Interleukin, Injection (LI) neoadjuvant extends overall survival in treatment-naïve locally advanced primary squamous cell carcinoma of the oral cavity/soft palate."

Avistone Announces Phase II Results for Vebreltinib, a c-Met Tyrosine Kinase Inhibitor (TKI) at the European Society for Clinical Oncology (ESMO) Congress

On October 23, 2023 Avistone Biotechnology Co., Ltd. ("Avistone" or "the Company"), a clinical-stage biotechnology company focused on precision oncology therapeutics, reported preliminary results of the Phase II KUNPENG study of Vebreltinib in Patients (Pts) with advanced Non-small cell lung cancer (NSCLC) Harboring MET (mesenchymal-epithelial transition factor) alterations (Poster# 1379P) at the European Society for Clinical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Madrid, Spain (Press release, Avistone Pharmaceuticals, OCT 23, 2023, View Source [SID1234636284]).

MET signaling is implicated in cell proliferation, migration, invasion, and survival. Genomic alterations in MET can manifest in driving oncogenesis in the form of MET exon 14 skipping mutations (METex14) or other activating mutations, MET gene amplification, gene fusion and MET protein overexpression. METex14 is an independent prognostic factor associated with poorer survival rates in patients with NSCLC. Avistone is developing Vebreltinib (also referred to as PLB1001, Bozitinib) to treat NSLCLC patients with MET exon 14 skipping alternations and in other potential indications in China.

As of August 9, 2022, 113 patients were enrolled in the China study, among whom 52 patients had METex14 skipping mutations (Cohort 1). Per the blinded independent review committee (BIRC), the primary endpoint of objective response rate (ORR) was 75% (95% CI: 61.1%-86.0%), with 39 participants achieving a complete response (CR) or partial response (PR). The treatment-naïve and previously treated patients displayed an ORR of 77.1% (95% CI, 59.9%-89.6%) and 70.6% (95% CI,44.0%-89.7%), respectively. The median progression free survival (PFS) was 14.1 months (95% CI, 6.4-17.9) and the median overall survival (OS) was 20.7 months (95% CI, 16.2-NE). Most of the TRAEs were grade 1/2.

"We are proud and excited to share data for Vebreltinib at this year’s ESMO (Free ESMO Whitepaper) Congress which has best-in-class potential for patients with MET aberrations in NSCLC," said Dr. Hepeng Shi, Chairman, CEO, and Founder of Avistone.

Electronic copies of the poster presented at the ESMO (Free ESMO Whitepaper) Congress are available upon request.

Salubris Biotherapeutics Presents Positive Initial Data from Phase 1b/2 Clinical Trial of JK08 at the European Society for Medical Oncology Annual Congress 2023

On October 23, 2023 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported that positive initial data from the first-in-human study evaluating JK08 in adults with solid tumors were presented in a poster session during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2023 (Press release, Salubris Biotherapeutics, OCT 23, 2023, View Source [SID1234636283]).

The presentation included safety data from 32 patients with relapsed or refractory solid tumors who received subcutaneous JK08 monotherapy once weekly in this Phase 1b/2 dose escalation study. At the dose levels evaluated to date, JK08 has been well tolerated, demonstrating preliminary disease stability and anticipated modulation of target immune cell populations in heavily pre-treated patients. Marked induction of NK and CD8+ T cells has been observed, and corresponding activation of these cell populations has been demonstrated through increased HLA-DR expression within these populations. More than 20% of heavily, pre-treated advanced metastatic cancer patients have remained on treatment for 3 months or longer demonstrating preliminary clinical benefit with monotherapy JK08, with the longest continuing therapy for 29 weeks. The most common adverse events have been mild to moderate (Grade 1 & 2) and consist of injection site reactions (ISRs), fatigue, pyrexia, anemia and nausea. No dose limiting toxicities or drug related adverse events leading to treatment discontinuations have been observed to date.

"JK08 combines CTLA-4 targeting with the effects of IL-15, with the aim of enhancing anti-tumor immune responses while managing potential side effects," said Sam Murphy, Chief Executive Officer of SalubrisBio. "We are pleased to see promising, dose-dependent pharmacodynamic activity and a favorable safety and tolerability profile in this heavily pre-treated patient population. While early, the data are very encouraging and we look forward to further evaluating JK08’s potential for solid tumor patients."

The ongoing Phase 1b/2, open label, dose escalation and cohort expansion study (NCT05620134) is designed to evaluate the safety and preliminary anti-tumor activity of JK08 in patients with unresectable locally, advanced or metastatic cancer. After dose escalation, monotherapy and combination dose expansion cohorts are planned. SalubrisBio plans to report additional data from this study at future medical meetings.

About JK08

JK08 is a recombinant fusion protein consisting of a CTLA-4-specific antibody and an IL-15 fusion domain. The JK08 design builds upon a breadth of clinical studies with CTLA-4 antibodies and recombinant IL-15 molecules, which together portend synergistic effects in an antibody fusion construct. The CTLA-4-specific antibody ipilimumab validated CTLA-4 as a target for cancer therapy, but response rates are limited. Analysis of clinical samples demonstrated that NK cell activity signatures and ADCC biomarkers correlate with ipilimumab responses. Recombinant IL-15 has exhibited potent stimulation of NK cell expansion and enhancement of ADCC in pre-clinical and clinical studies. Through the incorporation of a CTLA-4 antibody and IL-15 into a single molecule, JK08 can channel the potent immune stimulation of IL-15 through the CTLA-4 antibody domain towards depletion of T-regulatory cells and targeted reversal of immunosuppression which may contribute to cancer progression.