On April 25, 2025 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the conditional marketing authorization of zanidatamab, an investigational dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, as monotherapy for the treatment of adults with unresectable locally advanced or metastatic HER2-positive (IHC 3+)† biliary tract cancer (BTC) previously treated with at least one prior line of systemic therapy (Press release, Jazz Pharmaceuticals, APR 25, 2025, View Source [SID1234652162]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This positive CHMP opinion is a welcome step for physicians and patients in Europe who face a critical unmet need in HER2-positive biliary tract cancers, a rare and aggressive group of cancers with poor prognosis and limited treatment options," said Robert Iannone, MD., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "If approved, zanidatamab would be the first HER2-targeted therapy licensed for this difficult-to-treat cancer in the EU, marking an important milestone in addressing this unmet need. We look forward to the European Commission’s decision and the opportunity to provide a new treatment option for patients."

The CHMP recommendation is based on data from the Phase 2b HERIZON-BTC-01 trial, which evaluated zanidatamab in previously treated, inoperable, and advanced or metastatic HER2-positive BTC.2,3

While biliary tract cancers (BTCs), which include gallbladder cancer (GBC) and cholangiocarcinoma (CCA),4 account for less than 1% of all human cancers,5 CCA is the second most common primary liver cancer after hepatocellular carcinoma (HCC).5 It comprises approximately 10–15% of all primary liver cancers,4,5 and its global mortality rate has risen in recent decades.5

Most BTC cases are diagnosed at an advanced stage due to the vague or nonspecific nature of early disease symptoms,6 making curative surgery an option for only a minority of patients.5,7,8 Although chemotherapy and, more recently, immunotherapy-based combinations are used in the first-line setting, disease progression is common, and second-line treatment options are, in the absence of molecular analysis, largely limited to chemotherapy.5,7,9 HER2 overexpression or amplification has been identified as a distinct molecular subtype of BTC10,11 and is associated with a worse prognosis compared to HER2-negative BTC.12 Yet, no HER2-targeted therapies are currently approved for this indication in the European Union (EU).

The CHMP’s recommendation will now be reviewed by the European Commission which has the authority to approve medicines in all EU Member States, Iceland, Norway, and Liechtenstein, and is expected to make a final decision.

About Zanidatamab
Zanidatamab is a dual HER2-targeted bispecific antibody that simultaneously binds extracellular domains 2 and 4 on separate HER2 monomers (binding in trans). Binding of zanidatamab with HER2 results in internalization leading to a reduction of the receptor on the cell surface. Zanidatamab induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and tumor cell death.13

On November 20, 2024, in the United States, the U.S. Food and Drug Administration (FDA) granted accelerated approval of zanidatamab-hrii (Ziihera) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-approved test.14 This accelerated approval was granted based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the ongoing Phase 3 HERIZON-BTC-302 confirmatory trial.14

Zanidatamab is also being investigated in multiple other clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule. Jazz has rights to commercialize zanidatamab in the U.S., Europe, Japan and all other territories except for those Asia/Pacific territories that Zymeworks previously licensed to BeiGene, Ltd. [which are Asia (excluding Japan), Australia and New Zealand].

The FDA granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard-of-care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer.

About Biliary Tract Cancer
Biliary tract cancers (BTC), including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers worldwide and are often associated with a poor prognosis.5,7 Approximately 26% of patients with BTC are HER2-positive.10 The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers.7,15 Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.16 Most patients (>65%) are diagnosed with tumors that cannot be removed surgically.

On April 25, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches for precision immunotherapy, reported an upcoming clinical plenary oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Marengo Therapeutics, APR 25, 2025, View Source [SID1234652161]). The presentation will report updated clinical and translational findings from the ongoing Phase 1/2 trial (STARt-001) evaluating invikafusp alfa (STAR0602) in patients with anti-PD(L)1-resistant, antigen-rich solid tumors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The results highlight clinical pharmacology, selective immune activation, and RP2D selection in addition to demonstrating clinically meaningful anti-tumor activity and a well-characterized safety profile. The data also further support the advancement of the lead asset into Phase 2 development and confirm clinical efficacy.

"These encouraging data represent the first clinical proof of our precision T cell agonist approach to overcome anti-PD(L)1-resistant cancer, a therapeutic area with significant unmet need. Importantly, invikafusp monotherapy not only selectively engaged and expanded a key T cell subset in immunotherapy-resistant tumors, but also reinvigorated anti-tumor responses," said Ke Liu, M.D. Ph.D., Chief Development Officer of Marengo Therapeutics. "Based on the initial disease control and tumor regression rates observed, invikafusp has the potential to offer a promising new class of immunotherapy for patients who have exhausted checkpoint inhibitor therapy options."

"The initial clinical activity of invikafusp monotherapy in PD-1 resistant tumors is novel and important as a new approach to immunotherapy," said Bruce A. Chabner, M.D., Clinical Director Emeritus at Massachusetts General Hospital. "The ability of invikafusp to activate a specific subset of T cells in heavily pretreated cancer patients and achieve objective responses in tumors that have failed PD-1 inhibitors is clinically meaningful. These results may mark the beginning of a new class of novel T cell agonists in treating checkpoint resistant cancers with precision immune activation."

Invikafusp alfa is Marengo’s first-in-class, dual T cell agonist with a bi-specific antibody design to selectively activate the Vβ6 and Vβ10 subsets of T cells in vivo.

Key Findings from the Abstract (CT205):

Initial Clinical Activity (TMB-H subgroup at optimal biologic dose):
Six of the initial nine efficacy evaluable patients (67%) achieved disease control (2 confirmed partial responses (cPRs) and 4 with stable disease)
The cPRs were in MSS colorectal cancer with one response lasting ~12 months
Plenary oral presentation to include updated clinical results from initial data cut and additional patients
Clinical Pharmacology and Recommended Phase 2 Dose (RP2D):
RP2D was determined as 0.08 mg/kg Q2W, selected based on pharmacokinetics, pharmacodynamics, safety, and activity
Dose-dependent, selective expansion of peripheral CD8+ Vβ6/Vβ10 T cells, with ~600% average peak expansion at RP2D
Expanded Vβ T cells exhibited a memory phenotype and expressed cytotoxic effector molecules
Soluble markers of T cell activation (e.g., IFN-γ, sCD25) increased post-dosing; inflammatory cytokines (e.g., TNF-α, IL-6) remained limited below RP2D
Based on initial clinical and preclinical results, the U.S. Food and Drug Administration granted Fast Track Designation to invikafusp alfa for the treatment of patients with TMB-high colorectal cancer. The STARt-001 Phase 2 portion of the trial is ongoing and actively enrolling, focused on expanding into other antigen-rich tumors, including MSI-H and TMB-H tissue agnostic solid tumors.

Presentation Details

Title: Updated clinical results, recommended Phase 2 dose (RP2D) determination and translational study results for START-001: a Phase 1/2 trial of invikafusp alfa, a first-in-class TCR β chain-targeted bispecific antibody in patients with anti-PD(L)1-resistant, antigen-rich solid tumors
Abstract Number: CT205 (Late-breaking)
Session Title: Clinical Trials Plenary: Biologics and T-cell Engagers
Session Date and Time: Tuesday, April 29, 2025, 10:15 AM – 12:15 PM CT
Presenter: Ryan J. Sullivan, M.D., Massachusetts General Hospital

On April 25, 2025 Bantam Pharmaceutical, a drug discovery and development company targeting selective modulation of mitochondrial dynamics in cancer, reported solid tumor regression data from Bantam’s lead product candidate, BTM-3566 (Press release, Bantam Pharmaceutical, APR 25, 2025, View Source [SID1234652160]). These preclinical data will be shared in a poster presentation during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held from April 25-30, 2025 at the McCormick Place Convention Center in Chicago, Illinois. The poster highlights evidence of robust anti-tumor activity in a broad range of solid tumor models, as well as introduces FAM210B, a mitochondrial protein, as a potential biomarker for response.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

BTM-3566 is a first-in-class, small molecule cancer therapeutic which targets difficult-to-treat, aggressive tumors by activating OMA1-ATF4 Integrated Stress Response (ISR), a newly described mitochondrial homeostasis pathway. Previously, BTM-3566 was shown to have strong single-agent activity in both cell line and patient-derived xenograft (PDX) models of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL), regardless of cell of origin (COO) or genotype. The new data extend these findings to solid tumors and demonstrate that BTM-3566 has in vitro and in vivo activity across tumor types.

Key findings include:

BTM-3566 exhibits in vitro and in vivo activity in a broad range of solid tumor models
BTM-3566 drives tumor regression in models with low FAM210B RNA expression, supporting the use of FAM210B as a potential biomarker for response
Ectopic expression of FAM210B blocks drug activity in multiple models, suggesting a mechanistic role for the protein in mediating response
BTM-3566 demonstrates additive and synergistic activity in combination with other agents from multiple classes in preclinical models, including BH3 mimetics, supporting future combination strategies
"These findings provide important insight into the unique mechanism of our lead compound and support the potential for future patient selection using FAM210B expression," said Michael Stocum, President & CEO of Bantam Pharmaceutical. "We believe BTM-3566 holds promise not only as a monotherapy but also in combination with numerous approved anti-cancer agents, potentially expanding treatment options for patients with aggressive, hard-to-treat tumors. We intend to further explore these relationships as product development progresses."

Poster Presentation Details

Title: Selective pharmacological activation of the mitochondrial protease OMA1 inhibits tumor growth and induces regression in tumors expressing low levels of FAM210B
Presenter: Matthew Kostura, PhD, Chief Scientific Officer, Bantam Pharmaceutical
Session: Experimental and Molecular Therapeutics
Date/Time: Monday, April 28th at 3 p.m. to 6 p.m. ET
Abstract Number: 3032

The poster presentation will be available under the News & Resources section of the company’s website shortly after the event.

About BTM-3566

BTM-3566 is a novel, orally available small molecule designed to target a wide range of cancers, including both hematologic and solid tumors. Its initial clinical focus is on mature B-cell lymphomas, such as mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). In preclinical studies, BTM-3566 demonstrated potent anti-cancer activity, driving significant tumor regression – and in many cases, complete tumor elimination – in models resistant to standard treatments, including CAR-T cell therapy. BTM-3566 works by disrupting the mitochondrial function in tumor cells, triggering their natural cell death process (apoptosis). With its unique mechanism of action and strong preclinical data, Bantam also plans to expand clinical development into solid tumors, broadening its potential impact for patients with limited treatment options.

Currently, Bantam is conducting an ongoing Phase 1 clinical trial in both the U.S. and Canada evaluating BTM-3566 in relapsed/refractory mature B-cell lymphomas. For more information about the U.S. trial, visit ClinicalTrials.gov and search NCT06792734.

On April 25, 2025 Rgenta Therapeutics, a clinical-stage biotechnology company pioneering the development of a new class of oral small molecules targeting RNA and RNA regulation for oncology and neurological disorders, reported that preclinical data from its lead program, RGT-61159 were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting, which is being held from April 25-30, 2025, in Chicago, IL (Press release, Rgenta Therapeutics, APR 25, 2025, View Source [SID1234652159]). The data demonstrate robust anti-tumor activity of RGT-61159 in several cell-derived xenograft (CDX) models of AML and synergistic benefit when combined with standard of care for AML highlighting the potential of RGT-61159 to treat a broad AML patient population.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data presented at the AACR (Free AACR Whitepaper) meeting highlight the ability of RGT-61159 to reduce levels of both MYB RNA transcripts and correspondingly MYB protein in a dose dependent fashion, which translates to potent killing activity in cells that overexpress MYB," said Travis Wager, Ph.D. co-founder and chief scientific officer. "Importantly, we see robust antitumor activity with RGT-61159 across a range of AML models that carry genetic alterations that are common in patients with AML highlighting its potential to treat a broad AML patient population."

"Using RGT-61159, which specifically acts at the RNA level, we are able to address MYB which has been shown to function as an oncogenic driver in a variety of cancers including AML, colorectal cancer (CRC) and adenoid cystic carcinoma (ACC), and until now, has been a difficult target to drug," said Simon Xi, Ph.D., cofounder and chief executive officer of Rgenta. "Our ongoing Phase 1a/b clinical trial of RGT- 61159 in patients with relapsed or refractory ACC or CRC is advancing well and we look forward to broadening that program and initiating a new Phase 1/2 study of RGT-61159 in adults with AML/high risk myelodysplastic syndromes the second half of 2025."

In a poster titled RGT-61159, Best-in-class Oral Small Molecule Inhibitor of MYB via Selective RNA Splicing Alteration, Synergistic Anti-Tumor Activity When Combined with Standards of Care in Leukemia Disease Models Harboring AML Common Genetic Lesions, data were presented highlighting the close correlation between the elimination of MYB RNA and protein by RGT-61159 and its potent killing activity against leukemia and lymphoma cancer cell lines that over express MYB, demonstrating on-target therapeutic activity of this potent, orally available small molecule. RGT-61159 also inhibited AML cell proliferation and downregulated the expression of master oncogenes controlled by MYB, including MYC, BCL2, FLT3 and IDH1. Data from several CDX models of AML with genetic alterations seen commonly in AML, demonstrated the robust anti-tumor activity of tolerated doses of RGT-61159 and synergistic activity both in vitro and in vivo when administered in combination with agents used in AML standard of care.

About RGT-61159
RGT-61159 is an orally available small molecule designed to specifically modulate splicing of the transcription factor MYB resulting in the inhibition of the oncogenic MYB protein and potential cell death of the cancer cells that overexpress the MYB protein. MYB acts as a master regulator of cell proliferation, self-renewal, and differentiation processes and its aberrant expression has been demonstrated in multiple forms of human cancer including adenoid cystic carcinoma (ACC), acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (T-ALL), colorectal cancer (CRC), small cell lung cancer (SCLC) and breast cancer. Rgenta is evaluating RGT-61159 in an ongoing multi-center, open-label Phase 1a/b clinical trial in patients with advanced relapsed or refractory ACC or CRC. The Phase 1a/b study is designed to evaluate safety, tolerability, pharmacokinetics, target engagement and clinical efficacy of RGT-61159 in patients with ACC or CRC. Additional information about the Phase 1a/b clinical trial can be accessed at ClinicalTrials.gov (NCT06462183).

On April 25, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that its globally first-in-class PD-1/VEGF bispecific antibody, ivonescimab, has received approval from the National Medical Products Administration (NMPA) for its supplementary New Drug Application (sNDA) for use as a monotherapy for the first-line treatment of PD-L1-positive (TPS ≥ 1%) non-small cell lung cancer (NSCLC) in patients who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene mutations (Press release, Akeso Biopharma, APR 25, 2025, View Source [SID1234652158]). This indication marks Ivonescimab’s second major approval.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The sNDA approval is based on the breakthrough results of the AK112-303/HARMONi-2 Phase III study, which is a randomized, double-blind, controlled study that directly compared ivonescimab with pembrolizumab in first line PD-L1 positive NSCLC.

Ivonescimab demonstrated a statistically significant improvement in the trial’s primary end point, median progression-free survival (PFS) when compared to pembrolizumab, with a median PFS of 11.14 months, achieving a hazard ratio (HR) of 0.51 reducing the risk of disease progression or death by 49%.
An interim analysis of OS conducted at 39% data maturity (α=0.0001), indicated a clinically meaningful improvement in OS with ivonescimab compared to pembrolizumab, with a hazard ratio (HR) of 0.777, reflecting a 22.3% reduction in the risk of death.
Ivonescimab is the first therapy to achieve statistically significant positive results in a Phase III trial compared with pembrolizumab in a head-to-head setting.
Ivonescimab represents a new, more effective, and safer "chemotherapy-free" option for the first-line treatment of NSCLC.
Ivonescimab is the first bispecific antibody approved globally with a dual "cancer immunotherapy + anti-angiogenesis" mechanism. It has already shown significant positive results in three Phase III trials for lung cancer, including 1) treatment for EGFR-TKI-resistant NSCLC, 2) comparison with pembrolizumab in PD-L1-positive NSCLC, and 3) treatment in combination with chemotherapy versus tislelizumab in combination with chemotherapy in squamous NSCLC.

Professor Zhou Caicun, principal investigator of the HARMONi-2 trial, director of the Department of Oncology at the Shanghai East Hospital, Tongji University, commented:

"The Phase III HARMONi-2 study demonstrated that ivonescimab offers significant improvements in progression-free survival (PFS) and overall survival (OS) compared to pembrolizumab. This breakthrough provides a safer and more effective first-line treatment option for NSCLC, particularly beneficial for patients who need better efficacy or quality of life, or those who are not suitable for chemotherapy due to its side effects.

Ivonescimab has also gained widespread recognition in treating EGFR-TKI-resistant NSCLC. The recent Phase III trial combining ivonescimab with chemotherapy, compared to tislelizumab for squamous NSCLC, showed promising positive results. Ivonescimab is now positioned as a new standard of care for both first- and second-line treatment in lung cancer. We are optimistic about its continued success in global Phase III trials and its potential to redefine cancer treatment standards worldwide."

Dr. Xia Yu, Founder, Chairwoman, President, and CEO of Akeso, commented:

"We are thrilled to announce the approval of ivonescimab as a first-line treatment for PD-L1-positive NSCLC, a major breakthrough in cancer immunotherapy. This milestone is a result of the dedication of investigators, participants, and patients, and we sincerely thank all of them. We also appreciate the regulatory authorities for their efficient and diligent review, which enables us to offer this new treatment to patients in China.

Ivonescimab has shown superior efficacy over pembrolizumab in the HARMONi-2 Phase III trial, becoming the first therapy to achieve this globally. Positive results so far from three pivotal Phase III lung cancer trials further establish ivonescimab as a next-gen IO treatment with strong global potential.

The clinical data highlights ivonescimab’s exceptional efficacy and safety benefits for patients across various cancer types. Beyond lung, ivonescimab has demonstrated promising potential as first-line treatment for other key cancers, including breast, head and neck, biliary tract, and colorectal cancer, supported by, over 12 ongoing Phase III trials. Akeso, along with our partner Summit, are committed to advancing ivonescimab as a cornerstone of global cancer immunotherapy, aiming to provide safer, more effective treatment options for patients worldwide."