On December 11, 2024 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical-stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and other indications, reported a partnership with CareDx, Inc. (NASDAQ: CDNA) The Transplant Company who will perform pharmacokinetic analysis using its AlloCell solution in the ACHIEVE clinical trial (Press release, TC Biopharm, DEC 11, 2024, View Source [SID1234649058]).

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The ACHIEVE clinical trial is an adaptive, open-label, phase II study designed to evaluate the efficacy and effectiveness of TCB008, an allogeneic gamma delta T cell therapy for patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS).

CareDx is a leading precision medicine company focused on discovering, developing, and commercializing healthcare solutions for transplant patients and caregivers. CareDx’s AlloCell test, a sensitive solution for pharmacokinetic monitoring of allogeneic immune and stem cell therapies, will be used to evaluate the expansion and persistence of TCB008 in patients enrolled in the ACHIEVE trial.

It is expected that these expansion and persistence data will provide an understanding of the duration and effect of TCB008 Gamma Delta T-Cells in reconstituting the immune system of acute myeloid leukemia patients enrolled in the ACHIEVE trial.

"Our partnership with CareDx is a significant milestone," said Alison Bracchi, Executive Vice President of Clinical Operations at TC BioPharm. "The collaboration is pivotal to the development and optimization of TCB008 as a therapy for acute myeloid leukemia and other blood cancers."

"We are thrilled to continue to progress the science of allogeneic cell therapy for patients battling acute myeloid leukemia," said Marica Grskovic, PhD, CareDx Chief Strategy Officer. "This partnership builds upon our growth strategy to expand into hematology oncology with pharmacokinetic and monitoring assays for patients undergoing cell therapy."

On December 11, 2024 EORTC and Immunocore reported the randomisation of the first patient in the Phase 3 Adjuvant Trial in Ocular Melanoma (ATOM), investigating the safety and efficacy of tebentafusp as adjuvant treatment for uveal melanoma (Press release, EORTC, DEC 11, 2024, View Source [SID1234649044]).

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The primary objective of the open-label, international, multicentre trial – led by EORTC – will be to assess whether tebentafusp can prevent or delay relapse in patients with primary ocular (uveal) melanoma at high risk of relapse, as compared with observation. Tebentafusp is approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in 38 countries, under the brand name KIMMTRAK.

"I am delighted that the first patient on ATOM has been recruited. This milestone reflects a very significant effort by the EORTC melanoma group trials team, colleagues at Immunocore and our trial sites," said Professor Paul Nathan, ATOM study coordinator. "The study addresses a key question – whether the benefit seen with tebentafusp in HLA-A*02:01-positive patients with metastatic uveal melanoma will translate to a significant reduction in risk of relapse for patients who have received treatment for primary uveal melanoma and are at high risk of relapse."

The trial is expected to enrol 290 HLA-A*02:01-positive patients with uveal melanoma who have undergone definitive treatment by surgery or radiotherapy. Eligible patients will be randomised 1:1 to one of two arms: tebentafusp [as monotherapy] for six months or until disease relapse, or observation. Secondary objectives include overall survival, safety and tolerability, while exploratory objectives include evaluation of circulating tumour DNA (ctDNA) as a marker of residual disease, and a comparison of health-related quality of life.

Mohammed Dar, Chief Medical Officer at Immunocore, said: "Despite definitive local therapy, approximately 50% of patients will eventually relapse with metastatic disease. The goal of investigating adjuvant tebentafusp following primary treatment is to prevent future recurrence. Decreasing the likelihood of a patient relapsing following definitive therapy for their primary disease would be a groundbreaking advancement in treatment, given there are currently no standard treatment options available in this setting."

About the ATOM Phase 3 trial
ATOM (NCT06246149; 2023-510333-28-00) is an EORTC-led randomised open-label international multicentre Phase 3 superiority clinical trial aiming to prospectively assess whether adjuvant treatment with tebentafusp improves relapse-free survival as compared with observation. A total of 290 patients are expected to be enrolled within a span of three years, beginning in 13 countries, and with the potential for further expansion.

The goal of the experimental treatment strategy in the trial is to establish whether adjuvant tebentafusp can decrease the risk of relapse – compared to observation – in patients who have undergone definitive treatment for primary uveal melanoma and who are at high risk of relapse.

Patients included in the study must have undergone definitive treatment for primary ocular melanoma, by surgery or radiotherapy; be at high risk of relapse; be HLA-A*02:01 positive; have a good performance status (ECOG 0/1); and adequate organ function. Eligible patients will be randomised 1:1 to receive either active treatment with weekly tebentafusp [as monotherapy], or observation. Patients will receive tebentafusp for 6 months, or until relapse.

The secondary objectives are to compare overall survival and to further document the safety and tolerability of tebentafusp.

The exploratory objectives include the comparison of the health-related quality of life between the treatment arms and the evaluation of the role of circulating tumour DNA (ctDNA) as a biomarker for the presence of residual disease.

About Uveal Melanoma
Uveal melanoma is a rare disease arising from the pigmented uveal tract of the eye with an estimated incidence in Europe of 4.4 cases per million [i]. Up to 50% of people with uveal melanoma will eventually develop metastatic disease [ii]. Metastases usually appear within a median of three to five years after treatment of primary tumours, and treatment of metastatic disease is usually with palliative intent. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

Very few studies have tested the use of adjuvant treatment in uveal melanoma, and none have resulted in any change in the standard of care, reflecting a lack of active agents for this disease.

[i] Virgili G, Gatta G, Ciccolallo L, Capocaccia R, Biggeri A, Crocetti E, et al. Incidence of Uveal Melanoma in Europe. Ophthalmology 2007.
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[ii] Shields CL, Furuta M, Thangappan A, Nagori S, Mashayekhi A, Lally DR, et al. Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol 2009.
View Source

About ImmTAC molecules for cancer
Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognise and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumours, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumours, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumours.

On December 11, 2024 iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, reported a clinical update on its lead asset, roginolisib. Results from the completed Phase I DIONE-01 study are due to be presented at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) annual congress tomorrow, 12 December at 12:30 CET (presentation 164P) (Press release, iOnctura, DEC 11, 2024, View Source [SID1234649059]).

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Allosteric modulator of PI3Kδ, roginolisib, has a unique chemical structure and binding mechanism which makes it highly specific for PI3Kδ, giving it an advantageous pharmacology profile and an unprecedented safety profile compared to previous generations of PI3Kδ inhibitors.

Roginolisib is being investigated in solid and hematological malignancies including uveal melanoma (UM), a rare cancer of the eye. Eye melanoma is a rapidly growing market which is projected to be worth USD 9.56B by 2032[1].

The two-part Phase I study DIONE-01, firstly evaluated continuous daily dosing of roginolisib [at 10, 20, 40 and 80 mg] in 24 patients with pretreated solid tumors and follicular lymphoma (FL), and secondly evaluated a dose confirmation cohort in 20 UM patients.

Results from DIONE-01 show:

Study met its primary objective to determine the safety of the anticipated optimal biologically effective dose (BED): Roginolisib was well tolerated at the recommended Phase II dose (RP2D) of 80mg, with <7% Grade 3/4 treatment-emergent adverse events (TEAEs) considered to be related to roginolisib. TEAEs did not result in immune-related toxicity, or dose-limiting toxicity, in either solid tumor or hematological patients. In contrast to prior PI3Kδ inhibitors, roginolisib dosing did not require dose modifications.
Roginolisib is well tolerated over long periods of treatment, up to 4.5 years.
Median overall survival (OS) was 16 months for the 29 patients with UM treated with roginolisib, who had previously received a median of two prior therapies. This exceeds the median OS of 7 months observed in historical controls in patients receiving immunotherapies as second line treatment[2].
Median progression free survival (PFS) was 5 months for patients treated with roginolisib versus less than 3 months for historical controls2.
Clinical findings validate the mechanism of action of roginolisib: roginolisib reduces immune-suppressive immune cells and chemokines, UM-related tumor clones (ctDNA) and PI3K-related signaling indicating a rebalancing of the immune system.
Catherine Pickering, Chief Executive Officer of iOnctura, said: "The Phase I DIONE-01 data highlight the benefits of roginolisib for patients with uveal melanoma and advanced cancers. Roginolisib’s unique allosteric binding mechanism has translated into a differentiated beneficial clinical profile, including a doubling of overall survival compared to historical controls in uveal melanoma. We are delighted to announce these data support progression of roginolisib into a randomized Phase II study."

Professor Michele Maio, University of Siena and Principal Investigator of the roginolisib studies, added: "Being able to continue to investigate roginolisib in a randomized Phase II study is a positive step to understand more about this already well tolerated molecule. Roginolisib has given prolonged disease stabilization to patients with uveal melanoma who have exhausted all other therapeutic options. So far, these patients have maintained a good quality of life without major limitations. I’m looking forward to seeing what the Phase II trial delivers over the coming months."

Activation of trial sites for the Phase II OCULE-01 study (NCT06717126) investigating roginolisib versus investigator’s choice in the second-line+ treatment of uveal melanoma is ongoing.

On December 11, 2024 Hepion Pharmaceuticals, Inc. (Nasdaq: HEPA) (the "Company" or "Hepion"), a clinical stage biopharmaceutical company that had been developing a treatment for non-alcoholic steatohepatitis ("NASH"), hepatocellular carcinoma ("HCC"), and other chronic liver diseases, reported that it has entered into a termination agreement with Pharma Two B Ltd. which terminates the merger agreement between the two parties that was previously entered into on July 19, 2024 (Press release, Hepion Pharmaceuticals, DEC 11, 2024, View Source [SID1234649045]).

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Neither party will be required to pay the other a termination fee as a result of the mutual decision to terminate the agreement.

Hepion also announced that its previously announced special meeting of its stockholders scheduled for December 12, 2024 has been cancelled and that it has withdrawn from consideration by its stockholders the proposals set forth in the Company’s Definitive Proxy Statement on Form F-4 filed with the U.S. Securities and Exchange Commission on November 8, 2024.

On December 11, 2024 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported the publication of a pooled analysis evaluating sunvozertinib in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI)-resistant non-small cell lung cancer (NSCLC) in the official journal of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Lung Cancer (Press release, Dizal Pharma, DEC 11, 2024, View Source [SID1234649060]). The results of the analysis demonstrated that sunvozertinib exhibited promising antitumor activity and favorable safety profile, warranting future investigations into its potential in patients with EGFR mutated NSCLC who have developed resistance to EGFR TKIs.

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The analysis pooled data from three Phase 1 and 2 studies (WU-KONG1, WU-KONG2 and WU-KONG15). A total of 40 NSCLC patients with EGFR sensitizing mutations who had developed resistance to EGFR TKI treatment were enrolled, 90% of whom had received ≥ 3 prior lines of therapy. Eligible patients received sunvozertinib at doses ranging from 50 mg to 400 mg once daily. As of September 15, 2023, the key findings of the analysis were as follows:

The best objective response rate (ORR) was 27.5 %, and disease control rate (DCR) was 60 %.
The median duration of response (mDoR) and progression free survival (mPFS) were 6.5 months and 6 months, respectively.
Greater ORR of 55.6% was seen in patients with EGFR sensitizing and T790M double mutations (78% had received third-generation EGFR-TKI treatment in prior lines of therapy).
Sunvozertinib was well-tolerated, and the safety profile was consistent with previous reports.
"Resistance to chemotherapy or EGFR TKIs remains a major challenge in the management of EGFR mutated NSCLC. In clinical practice, EGFR-targeted therapeutic strategies are one of the main approaches to addressing EGFR-TKI resistance," said Mengzhao Wang, MD, PhD, at Peking Union Medical College Hospital, the first and corresponding author of the paper. "Sunvozertinib is an oral, irreversible EGFR TKI that targets a broad spectrum of EGFR mutations while maintaining high selectivity for wild-type EGFR. Previous studies suggested that sunvozertinib demonstrated anti-tumor activity in NSCLC patients with EGFR-sensitizing mutations, T790M mutations, and exon 20 insertion mutations. This new analysis further validated sunvozertinib’s potential in overcoming resistance to prior EGFR TKI treatments, warranting further investigation."

"Encouragingly, the pooled analysis has revealed the potential clinical value of sunvozertinib in EGFR TKI-resistant NSCLC," said Xiaolin Zhang, PhD, CEO of Dizal. "Confronted with the challenge of resistance to third-generation EGFR TKIs, we will continue to advance our exploration in this area, aiming to bring new treatment options to patients with EGFR mutated NSCLC."

About sunvozertinib (DZD9008)
Sunvozertinib is an irreversible EGFR inhibitor discovered by Dizal scientists targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, sunvozertinib received approval from NMPA to treat advanced NSCLC with EGFR exon20ins after platinum-based chemotherapies. The approval is based on the results of WU-KONG6 study, the pivotal study of sunvozertinib in platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The primary endpoint of the study was the confirmed overall response rate (cORR) as assessed by the Independent Review Committee (IRC) reached 60.8%. Anti-tumor efficacy was observed across a broad range of EGFR exon20ins subtypes, and in patients with pretreated and stable brain metastasis. In addition, sunvozertinib also demonstrated encouraging anti-tumor activity in NSCLC patients with EGFR sensitizing, T790M, and uncommon mutations (such as G719X, L861Q, etc.), as well as HER2 exon20ins.

Sunvozertinib showed a well-tolerated and manageable safety profile in the clinic. The most common drug-related TEAEs (treatment-emergent adverse event) were Grade 1/2 in nature and clinically manageable.

Two global pivotal studies are ongoing in ≥ 2nd line (WU-KONG1 Part B) and 1st line setting (WU-KONG28), respectively, in NSCLC patients with EGFR exon20ins.

Pre-clinical and clinical results of sunvozertinib were published in peer-reviewed journals Cancer Discovery and The Lancet Respiratory Medicine.