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.

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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."

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]).

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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.

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]).

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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.

On October 23, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that the full results of its Phase 2 BGBC008 study of bemcentinib and pembrolizumab in second line Non-Small Cell Lung Cancer (NSCLC) were presented during the European Society of Clinical Oncologists (ESMO) (Free ESMO Whitepaper) Annual Meeting 2023 (Press release, BerGenBio, OCT 23, 2023, View Source [SID1234636282]).

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The poster presentation is now available on BerGenBio’s website under →Pipeline→Scientific Publications.

In addition, on October 21st, Dr. Oddbjorn Straume, M.D., Ph.D., Assistant Professor, Clinical Science at the Haukeland University Hospital in Bergen, Norway presented results of the Investigator Led Study LBA52 of bemcentinib in addition to pembrolizumab or the targeted therapies dabrafenib/trametinib in 1L and 2L metastatic melanoma patients.

Cristina Oliva, Chief Medical Officer of BerGenBio, commented: "The full data analysis of the BGBC008 second line NSCLC study of bemcentinib in combination with the immune checkpoint inhibitor pembrolizumab showed promising long-term clinical benefits in patients regardless of their prior therapies, or PD-L1 status. In addition, the combination of bemcentinib with pembrolizumab was well tolerated with no new safety signals identified. These data provide a strong foundation for further clinical investigations of bemcentinib in NSCLC patients with high unmet needs, including those with STK11 mutations."

Dr. Oliva continued, "During the meeting, our collaborator, Dr. Oddbjorn Straume, also presented data on the combination of bemcentinib with standard of care therapies in first line and second line melanoma patients. While this small study failed to show the benefit of adding a selective AXL inhibitor to the treatment for melanoma patients, the results are consistent with the current limited understanding of the function of AXL in melanoma. In totality, these new data substantiate BerGenBio’s focused strategy on the treatment of first line NSCLC patients with STK11m patients in our on-going BGBC016 study."

On October 23, 2023 Hummingbird Bioscience, a data-driven precision biotherapeutics company discovering and developing transformative biologic medicines for hard-to-treat diseases, reported presentation of positive clinical data for the dose escalation part of the HMBD-001 Phase I/IIa trial (NCT05057013) at the European Society for Medical Oncology Congress 2023 (ESMO 2023). The trial is evaluating HMBD-001 as a monotherapy across various tumor types in the UK (Press release, Hummingbird Bioscience, OCT 23, 2023, View Source [SID1234636281]).

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As of the data cut-off on 8 September 2023, the trial had enrolled 23 heavily pre-treated patients across various tumor types where HER3 may play an important role. The dose escalation trial cleared six monotherapy cohorts with no dose-limiting toxicities (DLTs) and there were no treatment discontinuations due to related adverse events. Of the enrolled patients, 21 were evaluable for efficacy. Disease control rate (DCR) was 43% (9/21), with one patient achieving partial response with a 51% tumor shrinkage after four cycles of HMBD-001 treatment. HMBD-001 as monotherapy had a maximal half-life of 12 days in this trial.

"The favorable safety and tolerability profile of HMBD-001 and its monotherapy activity in biomarker-unselected cohorts are very encouraging and shows that HMBD-001 is an active antibody that effectively inhibits HER3 signaling, which has been shown to be important for cancer growth and survival. HMBD-001 is designed to be a best-in-class HER3 antibody with a differentiated mechanism of action, leveraging knowledge around HER3 biology built up by Hummingbird Bio over the years. To optimize clinical development, we are executing a phased strategy to demonstrate benefit in patients with gene signatures most likely to benefit from HMBD-001. We look forward to evaluating HMBD-001 in patients with squamous non-small cell lung cancer (sqNSCLC) and patients with HER3 aberrations, including NRG1 fusions, in the precision Phase Ib clinical trials recently initiated in Australia," said Jerome Boyd-Kirkup, Ph.D., Chief Scientific Officer, Hummingbird Bioscience.

"I am convinced that HER3 remains an important target for treating many cancers including prostate cancer, where it is implicated in treatment resistance through an interaction between tumor cell HER3 and hijacked white blood cells generating the protein activating it called NRG1. This clinical trial of a novel antibody targeting HER3 has demonstrated good tolerability and early evidence of anti-tumor activity, with an impressive and ongoing response in a patient with advanced pancreatic cancer who has clearly had clinical benefit. We envision that biology-based trials targeting HER3 deserve to be prioritized to continue this important effort," said Johann De Bono, Chief Investigator of the trial, Professor in Experimental Cancer Medicine at The Institute of Cancer Research, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust.

Stephen Nabarro, Ph.D., Interim Director of Cancer Research UK’s Centre for Drug Development said: "We are proud to have played an integral part in the significant progress that HMBD-001 has made in the clinic since we presented at ESMO (Free ESMO Whitepaper) 2022. A year on, and following successful completion of the dose escalation phase, we are seeing promising results emerging from the trial. Having observed anti-tumor activity in one patient already, we are excited about the opening of the metastatic castration-resistant prostate cancer (mCRPC) expansion arm and hope to continue on this path to bring HMBD-001 to patients with HER3-driven cancers." The Phase I/IIa clinical trial in the UK is sponsored and managed by Cancer Research UK’s Centre for Drug Development. This trial began enrolling in October 2021 and is ongoing in the UK.

Based on the encouraging clinical data from the Phase I clinical trial in the UK, Hummingbird Bioscience has initiated two Phase Ib trials studying HMBD-001 in combination with various agents, in patients with sqNSCLC (NCT05910827) and in patients with NRG1 fusions and HER3 mutations (NCT05919537), in Australia in Q3 2023.

Session Details
Date and time: 23rd October 2023, Monday, October 23, 2023, 12:00 – 13:00 CEST
Location: Hall 8

HMBD-001 Clinical Data Poster Details
Poster Title: A CRUK phase I/IIA, first in human dose-escalation and expansion trial of HMBD-001 (an anti-HER3 antibody) in patients with advanced HER3 positive solid tumours
Number: 687P
Presenter: Johann de Bono, Professor in Experimental Cancer Medicine at The Institute of Cancer Research, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust

HMBD-001 Pharmacokinetic Data Poster Details
Poster Title: Pharmacokinetics of HMBD-001, a human monoclonal antibody targeting HER3, a CRUK first-in-human phase I trial in patients with advanced solid tumours
Number: 688P
Presenter: Oladipo Idowu, Ph.D., Biomarker Research Associate, Cancer Pharmacology, Newcastle University Centre for Cancer

About HMBD-001

HMBD-001 is a clinical-stage IgG1 antibody designed to target HER3, discovered using Hummingbird Bioscience’s proprietary Rational Antibody Discovery (RAD) platform. We believe HMBD-001 is the only anti-HER3 antibody in development that has the potential to fully block both ligand-dependent and -independent HER3 activation and oncogenic signaling, by targeting a key epitope located at the interface where HER3 forms heterodimers with HER2 or EGFR. In preclinical models evaluating HMBD-001, superior affinity and more potent tumor growth inhibition compared to existing anti-HER3 antibodies were observed. HMBD-001 is currently in Phase Ib clinical trials for biomarker-selected indications with a strong scientific rationale, which includes squamous non-small cell lung cancer, NRG1 fusions, and HER3 mutations.