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InnoCare and KeyMed Jointly Announce the License Agreement with Prolium for CD20xCD3 Bispecific Antibody ICP-B02

On January 20, 2025 InnoCare Pharma (HKEX: 09969; SSE: 688428) and KeyMed Biosciences (HKEX: 02162) reported that the two companies, together with their joint venture, have jointly entered into an exclusive license agreement with Prolium Bioscience (Prolium) for the development and commercialization of ICP-B02 (CM355), a CD20xCD3 bispecific antibody (Press release, InnoCare Pharma, JAN 20, 2025, View Source [SID1234649776]).

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ICP-B02 binds to CD20 on the tumor cells and CD3 on the T cells, redirects and activates T cells to eradicate tumor cells through T-cell Directed Cellular Cytotoxicity (TDCC), which has demonstrated strong potential in both oncology and non-oncology fields.

Under the terms of the agreement, Prolium will have the exclusive right to develop, register, manufacture and commercialize ICP-B02 in the non-oncology field globally and in the oncology field in ex-Asia regions.

InnoCare and KeyMed will receive aggregate payments of up to $520 million, including upfront and near-term payments and other payments subject to the achievement of certain clinical, regulatory and commercial milestones, as well as a minority equity stake in Prolium. InnoCare and KeyMed are also eligible to receive tiered royalties on future net sales of any product resulting from the collaboration.

Prolium is a Delaware company funded and backed by RTW Investments, LP, a New York-based, global, full life-cycle investment firm that focuses on identifying transformational and disruptive innovations across the biopharmaceutical and medical technologies sectors.

About ICP-B02 (CM355)

ICP-B02 is a CD20×CD3 bispecific antibody jointly developed by InnoCare and KeyMed. A Phase I/II clinical trial in China is ongoing to assess the safety, tolerability, PK and the preliminary anti-tumor activity of ICP-B02 in relapsed / refractory Non-Hodgkin lymphoma (NHL). The study has shown promising early results in both intravenous (IV) and subcutaneous (SC) formulations, particularly in patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Based on the encouraging results of ICP-B02 single agent, a dose expansion study of ICP-B02 in combination with other immunochemotherapies is planned to target earlier lines of treatment for NHL patients. The IND for the combination therapies has been approved.

CARsgen’s Allogeneic CD38 CAR-T Therapy Administers First Dose in an Investigator-Initiated Trial

On January 20, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that KJ-C2320, an allogeneic CAR T-cell therapy targeting CD38, has administered the first dose to a patient in an investigator-initiated trial (IIT) (Press release, Carsgen Therapeutics, JAN 20, 2025, View Source [SID1234649775]).

KJ-C2320 is developed based on CARsgen’s THANK-uCAR platform. An investigator-initiated trial is ongoing in China to evaluate KJ-C2320 for the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).

About THANK-uCAR

THANK (Target to Hinder the Attack of NK cells)-uCAR is CARsgen’s proprietary technology to generate allogeneic CAR-T cells with improved expansion and persistence by modifying donor-derived T cells. To minimize graft versus host disease (GvHD) and host versus graft response (HvGR) from allogeneic T cells, we disrupt the genomic loci encoding TCR and beta-2 microglobulin (B2M) to eliminate surface expression of the TCR or the human leukocyte antigen class I (HLA-I), an approach that has been validated by previous research. However, natural killer (NK) cells can attack T cells without HLA-I expression, which then limits the expansion and persistence of the allogeneic CAR-T cells. To protect the allogeneic CAR-T cells from the patient’s NK cells’ attacks, we arm these TCR-/B2M-T cells with a CAR that recognizes NKG2A to hinder the NKG2A-positive NK cell rejection of the CAR T cells and therefore allow the THANK-uCAR-T cells to resist the attack by NK cells. Clinical studies have demonstrated that the BCMA CAR-T therapy developed on the THANK-uCAR platform can expand in patients achieving complete response to levels comparable to autologous CAR-T, showing preliminary evidence of controllable safety and promising efficacy.

European Commission expands Jemperli (dostarlimab) plus chemotherapy approval to all adult patients with primary advanced or recurrent endometrial cancer

On January 20, 2025 GSK plc (LSE/NYSE: GSK) reported the European Commission has approved Jemperli (dostarlimab) in combination with chemotherapy (carboplatin and paclitaxel) for first-line treatment of adult patients with primary advanced or recurrent endometrial cancer who are candidates for systemic therapy (Press release, GlaxoSmithKline, JAN 20, 2025, View Source [SID1234649774]). This approval broadens the previous indication for Jemperli plus chemotherapy in the European Union (EU) to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours, which represent approximately 75% of patients diagnosed with endometrial cancer and who have limited treatment options.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "For the first time, all patients with primary advanced or recurrent endometrial cancer in the EU have an approved immuno-oncology-based treatment that has shown a statistically significant and clinically meaningful overall survival benefit. We’re proud Jemperli continues to redefine the treatment landscape for patients."

Dr Mansoor Raza Mirza, Chief Oncologist, Copenhagen University Hospital, Denmark, and RUBY principal investigator said: "Clinicians have been waiting for years for an immuno-oncology-based option that can meaningfully improve overall survival outcomes for patients with MMRp/MSS primary advanced or recurrent endometrial cancer. The expanded approval represents a significant advance that delivers on this hope, now for patients with both dMMR/MSI-H and MMRp/MSS tumours."

The European Commission’s approval to expand the use of Jemperli plus chemotherapy is based on results from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a clinically meaningful and statistically significant overall survival (OS) benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.

At the 2.5-year landmark, the chance of being alive was 61% (95% CI: 54-67) for patients in the Jemperli plus chemotherapy group (245 patients) compared to 49% (95% CI: 43-55) in the chemotherapy group (249 patients). In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.1 The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli plus carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse reactions (≥ 10%) in patients receiving Jemperli plus chemotherapy were rash, rash maculopapular, hypothyroidism, pyrexia, alanine aminotransferase increased, aspartate aminotransferase increased and dry skin.

OS data were presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer on 16 March 2024, and were published in Annals of Oncology on 9 June 2024. The label for Jemperli plus chemotherapy in the US was expanded to all adult patients with primary advanced or recurrent endometrial cancer in August 2024.

About endometrial cancer 
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries,2 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.3 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.4 In Europe, approximately 121,000 people are estimated to be diagnosed with primary advanced or recurrent endometrial cancer each year.5 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.6 Among patients with primary advanced or recurrent endometrial cancer, approximately 75% have MMRp/MSS tumours.7

About RUBY  
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of 785 patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.   

In Part 1, the dual-primary endpoints are investigator-assessed progression-free survival (PFS) based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma. 

In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.  

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.

About Jemperli (dostarlimab)
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes.

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This includes patients with MMRp/MSS and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Additionally, Jemperli is indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 
 
Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist. 

Important Information for Jemperli in the EU
Indication
Jemperli is indicated:

in combination with carboplatin and paclitaxel, for the first-line treatment of adult patients with primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy;
as monotherapy for treating adult patients with mismatch repair deficient (dMMR)/ microsatellite instability-high (MSI-H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.
Refer to the Jemperli EMA Reference Information for a full list of adverse events and the complete important safety information in the EU.

Stamford announces positive results from Phase 2 Study of SP-002 in combination with 4-weeks of vismodegib in multi-lesional Basal Cell Carcinoma patients

On January 17, 2025 Stamford reported positive results for its ASN-002-003 multi-lesional clinical trial (NCT 04416516. Protocol No ASN-002-003) evaluating SP-002, an Adenovirus-5 replication deficient vector encoding human Interferon- g in combination with vismodegib (a Hedgehog Pathway Inhibitor) in subjects presenting with mul/ple BCCs (Press release, Stamford Pharmaceuticals, JAN 17, 2025, View Source [SID1234649770]). The collected demographic data revealed subjects that were presenting with multiple BCCs had a history of multiple BCCs (and oLen a family history of multiple BCCs), thus representing a high-burden disease pa/ent group. 1 Three cohorts (cohorts 1, 2, 6) were evaluated in ASN-002-003. 2 Cohort 1 (1 target lesion) and Cohort 2 lesions (up to 3 target lesions)2 were both treated with 1.0e11vp/lesion and 4-weeks of vismodegib. 3 Cohort 6 (up to 3 target lesions) were treated with 1.5e11vp/lesion and 4-weeks of vismodegib. Cohort 1, 2 and 6 achieved a complete histological clearance rate (CHC) of 75%, 53% and 48% in the Intent to treat (ITT) population (46 lesions evaluated). A Histopathologic criteria4 predic/ve of poor response to SP-002 was first iden/fied in the ASN-002-001 (NCT02550678. Protocol No ASN-002-001) clinical study and was also evaluated in the current study (ASN-002-003). In ASN-002-003, all lesions lacking these histopathologic features predictive of poor response (n=23) across Cohorts 1, 2 and 6, achieved complete histological clearance, resul/ng in a CHC rate of 100%.

The combination of SP-002 plus vismodegib was consistent with safety profiles of the individual agents with no new safety signals observed. Adverse events were generally mild to moderate in severity, no grade 4 or 5 events were observed. The observed safety profile for eligible subjects treated with weekly injections for local reactions was as follows: No Adverse Events (AEs): 15.2%; Grade 1 AEs: 34.8%; Grade 2 AEs: 47.8%; and Grade 3 AEs: 2.2%. Local AEs included swelling, erythema and ulceration/scabbing at the injection site.

Based on the study data, all participants experienced at least one treatment-emergent adverse event (TEAE), with 95.2% repor/ng events potentially related to vismodegib. Common systemic adverse events included muscle spasms (52.4%), nausea (19.0%), and fa?gue (14.3%), consistent with the known safety profile of the drug. While most AEs were mild to moderate, they were carefully monitored to ensure participant safety and provide insights into vismodegib’s tolerability.

"We are very pleased with these positive results from the Phase 2 study demonstrating the safety and efficacy of our gene therapy for patients with multiple nodular and superficial BCCs. We are particularly excited that the histopathologic criteria, which would allow responsive patients to be identified at screening and used for patient selection. This histopathologic criterion was first noted in the ASN-002-001 clinical study and has now been successfully reproduced in ASN-002-003. We believe this enables us to develop a useful treatment option for patients with nodular BCC and addresses the important need for a non-surgical option for those with BCCs in the H-zone or for those who are not ideal candidates for surgery." Dr Clement Leong (PhD), CEO of Stamford Pharmaceuticals.

"We are excited to have a novel approach that seeks to address the significant unmet needs in the treatment of basal cell carcinoma, particularly for patients managing multiple lesions. This innovative solution may hold promise for tumors located in the H-zone or other high-risk areas of the body, where effective and targeted non-surgical care options are critically important." Dr Sherrif F. Ibrahim, (MD, PhD), Rochester Dermatologic Surgery, P.C. "These results highlight the potential of this product to substantially enhance clearance rates compared to existing non-surgical treatment options for nodular BCC." Professor John Lear, MB ChB, MD, FRCP (UK), Mid Cheshire Hospitals NHS foundation trust, UK.

Analyses of the full Phase 2 dataset are ongoing and additional biomarker/translational research findings are to be presented at upcoming medical conferences. SP-002 has received Orphan Drug designations from the U.S. Food and Drug Administration (FDA). Stamford plans to discuss these findings with regulatory authorities in the coming months to prepare for a pivotal late-stage clinical study.

U.S. Food and Drug Administration Approves FoundationOne®CDx as a Companion Diagnostic for OJEMDA™ (tovorafenib) to Treat the Most Common Form of Childhood Brain Tumor in Pediatric Patients

On January 17, 2025 Foundation Medicine, Inc. reported that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneCDx to be used as a companion diagnostic for Day One Biopharmaceuticals’ OJEMDA, a type II RAF inhibitor, for the treatment of patients six months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation (Press release, Foundation Medicine, JAN 17, 2025, View Source [SID1234649769]). FoundationOne CDx is the first and only companion diagnostic for OJEMDA.

pLGG is the most common brain tumor diagnosed in children.1,2 In this patient population, a BRAF alteration is detected in up to 75 percent of cases. Previously, no FDA-approved treatment options were available targeting tumors harboring BRAF fusions, which represent 80% of BRAF altered patients.3,4,5,6,7

"Foundation Medicine is proud to partner with Day One to help healthcare providers connect pediatric patients and families with this treatment option," said Mia Levy, M.D., Ph.D., chief medical officer at Foundation Medicine. "Our high-quality tissue-based companion diagnostic test is uniquely capable of detecting both BRAF V600 mutations and fusions which enables providers to gain the complete genomic picture of their patient’s tumor and guide treatment decision making."

Foundation Medicine has sequenced over 2,200 pediatric central nervous system tumors8 and is the only company to offer both tissue and blood-based comprehensive genomic profiling tests that are approved by the FDA. Using a tissue sample, the FDA-approved FoundationOne CDx test analyzes more than 300 cancer-related genes in a patient’s tumor. Foundation Medicine is the global leader in approved companion diagnostic indications. Foundation Medicine also has 40% of all approved companion diagnostic indications for next-generation sequencing (NGS) testing in the United States and Japan.9,10

"Historically, pediatric patients with pLGG have faced overwhelming side effects, both near- and long-term, from aggressive treatments like chemotherapy and radiation," said David Arons, president and chief executive officer at the National Brain Tumor Society. "We are thrilled to see that there are now additional treatment options available for these children, as well as an FDA-approved companion diagnostic test to help identify more patients who may benefit from Day One’s therapy."