On March 11, 2024 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported that its Phase 1 clinical trial of CD19 oncolytic virotherapy drug candidate onCARlytics (on-CAR-19, CF33-CD19 HOV4) has cleared its first cohort within the intratumoural monotherapy arm of the study and is therefore ready to commence combination dosing solid tumour patients with CD19 targeting drug blinatumomab (Blincyto marketed by Amgen) (Press release, Imugene, MAR 11, 2024, https://mcusercontent.com/e38c43331936a9627acb6427c/files/29d98be7-23cc-5260-9e48-e0e4a65ee3ac/Phase_1_onCARlytics_Trial_Advances_to_Combination_Arm.pdf [SID1234640982]).

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Known as OASIS, the first-in-class clinical trial is targeting adult patients with advanced or metastatic solid tumours, and aims to evaluate the safety and efficacy of two routes of administration, intratumoural (IT) injection and intravenous (IV) infusion, either alone, or in combination with blinatumomab.

The trial is titled: "A Phase I, Dose Escalation and Dose Expansion, Safety and Tolerability Study of onCARlytics (CF33-CD19), Administered Intravenously or Intratumorally in Combination with Blinatumomab in Adults with Advanced or Metastatic Solid Tumors." See View Source

The combination arm of the study will see onCARlytics combined with CD19 targeting bispecific monoclonal antibody blinatumomab (marketed as Blincyto by Amgen which currently is specifically approved only for liquid blood cancers). OnCARlytics has the potential to target and eradicate solid tumours that otherwise cannot be treated with Blincyto therapy alone and will represent a paradigm shift in solid tumour treatment.

OASIS is a dose escalation trial that will be conducted across multiple sites across the United States, with 52 patients proposed to take part in the trial.

Imugene Managing Director and CEO Leslie Chong said:

"It’s once again a credit to our team and collaborators to see yet another study progressing positively and on schedule. Completion of this first monotherapy intratumoural cohort where ovarian, breast and melanoma patients were dosed paves the way for us to move into an important combination dosing with Blincyto, where we’ll be eager to see the greater potential of onCARlytics in targeting and eradicating solid tumours."

OnCARlytics is a CD19-expressing oncolytic virus that enters tumour cells and forces them to express the CD19 protein on the cell surface, presenting a target for CD19 targeting therapies.

On March 10, 2024 RemeGen Co. Ltd.("RemeGen" or "the Company") (9995.HK, 688331.SH), a commercial-stage biotechnology company, reported an oral presentation on an interim analysis of the evaluation of the Company’s proprietary Disitamab Vedotin (RC48), an investigational anti-HER2 antibody-drug conjugate (ADC) targeting prevalent solid tumor cancers with significant unmet medical needs, at the European Congress on Gynaecological Oncology (ESGO 2024 Congress) held in Barcelona from March 7-10, 2024 (Press release, RemeGen, MAR 10, 2024, View Source [SID1234640983]).

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A Phase II, open-label, multicenter basket design study (NCT04965519) is currently underway to evaluate the effectiveness and safety of RC48 monotherapy in the treatment of HER2-expressing gynecologic malignancies. The cervical cancer cohort includes patients with recurrent or metastatic cervical cancer who have progressed on at least 1L anti-tumor therapy and have HER2 IHC ≥1+. The treatment regimen consists of RC48 monotherapy administered at a dose of 2 mg/kg Q2W. The primary endpoint is objective response rate (ORR) by Independent Review Committee, with secondary endpoints including ORR by Investigator, duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety.

As of October 31, 2023, 25 patients with cervical cancer were enrolled with a median age of 56 years (range: 35-66). Most patients (64%) had a baseline ECOG performance score of 1. 18 patients had a primary FIGO stage of IIB or higher. 16 (64%) patients had squamous cell carcinoma, and 9 (36%) had adenocarcinoma. Among the 22 efficacy evaluable patients,

The ORR was 36.4% (8/22). The confirmed ORR was 31.8% (7/22), the DCR was 86.4% (19/22), and the median time to response was 1.5 months.
The mDoR was 5.52 months, and the mPFS was 4.37 months.
The most common treatment-related adverse events (TRAEs) included an increase in ALT (56%), an increase in AST (56%), and a decrease in white blood cell count (52%). Two patients (8%) experienced SAEs, and there were no deaths related to RC48. In conclusion, RC48 demonstrates a manageable safety profile and positive efficacy in HER2-expressing r/m cervical cancer patients, suggesting it to be a promising new treatment for HER2-expressed cervical cancer.

Dr. Jianmin Fang, CEO of RemeGen, commented, "ESGO congress is a unique opportunity for professionals from around the world to share and discuss their latest medical and scientific developments in their gynecological cancers research, treatment, and care. I am delighted to share an oral presentation on the evaluation of our proprietary ADC Disitamab Vedotin at ESGO 2024. It marks RemeGen’s commitment to continued innovation and advancement in the field of cervical cancer treatment, and we strongly believe that the results of RC48 will bring new hope to cervical cancer patients."

Cervical cancer is one of the most common gynecological malignancies, with the latest cancer report in China in 2022 showing the 5-year progression-free survival (PFS) rate of patients with late-stage recurrent or metastatic cervical cancer to be only about 15%. Current treatment options for patients with recurrent or metastatic cervical cancer are limited to immunotherapy and chemotherapy (ORR ranging from 14.6% to 26.8%), indicating there are significant unmet clinical needs.

On March 8, 2024 Sorrento Therapeutics reported the US Bankruptcy Court gave an order approving the sale of the certain assets of the company (Press release, Sorrento Therapeutics, MAR 8, 2024, View Source [SID1234651027]). The debtor has been authorized to sell its certain assets to Vivasor, Inc., for a purchase price of $15.5 million in cash including outstanding DIP loan and $5 million promissory note pursuant to the asset purchase agreement dated March 8, 2024. The debtor?s assets include all equity interests held by debtor in certain subsidiaries.

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Justin Rawlins and Sahand Moarefy of Paul Hastings LLP acted as counsels for the buyer.

On March 8, 2024 Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences Inc., a global fully-integrated clinical-stage biotech company, reported that Nature Communications – peer-reviewed, open access, scientific journal – published a manuscript describing the pre-clinical development of ISB 1442, a CD38 and CD47 Bispecific Biparatopic Antibody Innate Cell Modulator (online manuscript available here) (Press release, Ichnos Sciences, MAR 8, 2024, View Source;utm_medium=rss&utm_campaign=ichnos-glenmark-innovation-reports-the-publication-in-nature-communications-of-the-preclinical-development-of-isb-1442-bispecific-antibody-for-treatment-of-relapsed-refractory-multiple-myeloma [SID1234642877]). ISB 1442 is currently being tested in a Phase I clinical trial in relapsed refractory multiple myeloma.

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"The acceptance of our manuscript by Nature Communications signifies the high quality of research conducted at Ichnos Glenmark Innovation, particularly in the challenging field of multiple myeloma. Our ongoing Phase I trial is a testament to our commitment to advancing care for patients battling this complex disease. We are eager to present further data to the medical community before the end of this year, highlighting our continuous efforts to innovate and improve patient outcomes," said Cyril Konto, President, CEO and Board Member of Ichnos Glenmark Innovation.

ISB 1442 is a multispecific antibody, rationally designed to harness innate immunity to treat CD38+ hematologic malignancies. ISB 1442 antibody is unique due to three features: (i) it uses two distinct Fab arms to target the CD38 tumor associated antigen (biparatopic approach), allowing for improved Complement Dependent Cytotoxicity (CDC) and improved binding to tumor cells when an antigen is downregulated; (ii) it blocks the CD47 ‘don’t eat me’ signal to counteract tumor escape from phagocytosis, leveraging selective avidity-induced binding to CD38+ tumor cells, thereby avoiding off-tumor targeting; and (iii) it is equipped with the Fc mutations enhancing effector mechanisms (CDC, Antibody Dependent Cell Cytotoxicity and Antibody Dependent Cell Phagocytosis).

The flexibility of the BEAT(Bispecific Engagement by Antibodies based on the TCR) platform enabled straightforward integration of all these features into a single antibody molecule.

Impactful pre – clinical study outcome
On cell lines, ISB 1442 showed superior tumor cell killing against daratumumab or to the combination of daratumumab with an anti-CD47 mAb (hu5F9). This implies that the engineering and architecture of ISB 1442 possesses improved effector functions compared to standard anti-CD38 monoclonal antibodies as well as their combination with CD47 blocking agents.

ISB 1442 consistently demonstrated superior tumor growth inhibition compared to daratumumab in preclinical mouse models in vivo and higher killing of tumor cells in primary multiple myeloma patient’s samples ex vivo, including in patients that relapsed from anti-CD38 therapies. This suggests that ISB 1442 could be effective as monotherapy as well as salvage therapy. Altogether, ISB 1442 may represent an improved therapeutic option available for the treatment of multiple myeloma patients relative to other monospecific anti-CD38 antibodies.

On March 8, 2024 Agendia, Inc., reported that it will share new data from the ongoing prospective, observational FLEX Trial (NCT03053193) in two poster presentations at the 41st Annual Miami Breast Cancer Conference (MBCC), taking place March 7 – 10th, 2024 (Press release, Agendia, MAR 8, 2024, View Source [SID1234640976]).

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The first poster, titled MammaPrint and BluePrint predict anthracycline chemosensitivity in patients with HR+HER2-early-stage breast cancer enrolled in FLEX, (Audeh, W., et al.), investigates the associations between MammaPrint and BluePrint classifications, therapy regimen, and the likelihood of achieving a pathologic Complete Response (pCR). Researchers looked at patients who had hormone receptor-positive (HR+), Human Epidermal Growth Factor Receptor (HER) 2-negative early-stage breast cancer – categorized as MammaPrint High Risk – who had been treated with either a combination of two (taxane and cyclophosphamide, TC) or three (TC with anthracycline, AC-T) types of neoadjuvant chemotherapy. Patients were then further stratified into MP High 1 and High 2 categories, and further stratified by BluePrint subtype of Luminal and Basal. Results showed that patients with MP High 2 tumors, including Luminal B and Basal subtypes, are more likely to achieve a pCR in response to AC-T, while the addition of anthracycline to the therapy regimen does not appear to improve pCR rates for patients with MP High 1, Luminal B-type tumors.

The second poster, titled Prediction of chemotherapy benefit by MammaPrint in patients with HR+HER2-early-stage breast cancer from real-world evidence studies (Audeh, W., et al.), used data from patients with HR+ HER2-negative early-stage breast cancer enrolled in the FLEX and NBRST trials to generate a prediction of the magnitude of chemotherapy benefit based upon a patient’s genomic risk, looking at the MammaPrint index more closely as a continuous variable. Researchers examined the association of the MammaPrint index with benefit from chemotherapy by evaluating two clinical endpoints, the likelihood of pCR in response to neoadjuvant chemotherapy, and the five-year outcome among patients who received chemotherapy and endocrine therapy or endocrine therapy alone.

Consistent with results found in the landmark MINDACT trial, this study showed that the MammaPrint index demonstrates strong efficacy in predicting low chemosensitivity in Low Risk and Ultra Low Risk tumors, reinforcing that these groups do not derive significant chemotherapy benefit. However, it was also observed that chemotherapy effectiveness increased as MammaPrint risk increased in High 1 and High 2 tumors, as evidenced by both pCR rates and 5-year outcomes, demonstrating that the overall benefit of chemotherapy increases as MammaPrint risk increases. Taken together, these findings indicate the utility of MammaPrint to predict neoadjuvant and adjuvant chemotherapy benefit in this patient population.

"In this unique real world evidence FLEX study, we were able to look at chemosensitivity for patients who had received neoadjuvant treatment and the chemo benefit for patients who are treated with systemic therapy after surgery, showing that MammaPrint is predictive of chemotherapy benefit in both cases. The FLEX Trial, with over 16,000 women enrolled, is now allowing us to look at clinical outcomes as well as analyzing whole transcriptome data," said William Audeh, MD, MS, Chief Medical Officer of Agendia. "The data we’re sharing at the Miami Breast Cancer Conference confirms that gene expression profiling with these assays identify who may benefit from chemotherapy, and may prove helpful in regimen selection as well. We look forward to further exploring the capabilities of MammaPrint and BluePrint for women across the entire spectrum of breast cancer risk and subtype."

The goal of Agendia’s research is to increase the likelihood of managing each individual’s cancer diagnosis by delivering a customized treatment plan to the patients most likely to benefit based on the unique features of their tumor.