On October 23, 2025 HanchorBio Inc. (TPEx: 7827), a global clinical-stage biotechnology company developing next-generation immunotherapies, reported that its manuscript describing the discovery and preclinical development of HCB101, an engineered SIRPα-Fc fusion protein, has been published in the Journal of Hematology & Oncology (SCI Impact Factor 40.4; for reference, leading journals in the field of immuno-oncology include Journal of Clinical Oncology (impact factor 41.9), The Lancet Oncology (35.9), and Nature Cancer (28.5)).

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The publication, titled "HCB101: A Novel Potent Ligand-Trap Fc-fusion Protein Targeting the CD47-SIRPα Pathway with High Safety and Preclinical Efficacy for Hematological and Solid Tumors," describes the rational protein engineering that enabled HCB101 to restore macrophage-mediated phagocytosis and bridge innate and adaptive immune responses while reducing red blood cell binding. In preclinical studies, HCB101 showed broad activity across more than 80 xenograft and PDX tumor animal models with a safety profile that differs from first- and second-generation CD47-targeting agents.

Notably, a US competitor focusing on CD47/SIRPα published findings in JHO in November 2020, reporting on a third-generation anti-CD47–SIRPα therapy. This underscores the journal’s strong recognition within the field. The continued publication of anti-CD47 biologics in JHO highlights both the scientific importance of ongoing advancements and the journal’s role as a leading international platform for preclinical and translational research on anti-CD47 therapies.

"Publication in the Journal of Hematology & Oncology affirms the scientific rigor and innovation behind HCB101 and emphasizes its differentiated preclinical foundation," said Scott Liu, PhD, Chairman, CEO, and Founder of HanchorBio. "Importantly, these insights are being directly translated into clinical studies: combined with standard-of-care, HCB101 has demonstrated a clear dose-dependent efficacy profile in 2L gastric cancer, culminating in a nearly 90% partial response rate at 5.12 and 8.0 mg/kg. In parallel, we have now escalated monotherapy dosing to 30 mg/kg without safety concerns. These milestones highlight HCB101’s potential to serve as a backbone immunotherapy across solid tumors and hematologic malignancies and lay the groundwork for expanding into autoimmune indications where CD47-SIRPα biology is also potentially useful in creating a new B-cell depletion therapy."

Clinical Progress Strengthens Differentiated Best-in-Class Profile
HCB101 is currently being evaluated in multinational Phase 1 and Phase 1b/2a trials:

Monotherapy (HCB101-101, NCT05892718):
The Safety Review Committee (SRC) has reviewed the safety data up to 30 mg/kg weekly and found no dose-limiting toxicities, confirming a wide therapeutic window. Early signs of efficacy included two confirmed partial responses (PRs) in head and neck squamous cell carcinoma and marginal zone lymphoma, along with stable disease (SD) in nine patients, including over 40 weeks of disease control in platinum-resistant ovarian cancer.
Combination (HCB101-201, NCT06771622):
In the triplet regimen for 2L-gastric cancer (HCB101 + ramucirumab + paclitaxel), emerging activity was first observed at 2.56 mg/kg, where evaluable patients achieved SD with modest tumor shrinkage, averaging a 6% reduction in tumor size in the dose cohort. At 5.12 mg/kg, all three evaluable patients achieved confirmed PRs (33%–46% tumor reductions). At 8.0 mg/kg, all three evaluable patients have now achieved confirmed PRs (tumor shrinkage up to -78%) after extended follow-up. Together, these results represent a nearly 90% confirmed response rate (6 of 7 patients) at ≥ 5.12 mg/kg dose level — a striking outcome in a setting where the typical overall response rate (ORR) for the SOC is only 26.5%.
"The data now published in JHO validate the design strategy that made HCB101 possible – balancing high efficacy with a clean safety margin where earlier CD47-targeting agents failed," added Wenwu Zhai, PhD, Chief Scientific Officer of HanchorBio. "Seeing those preclinical insights translate into durable monotherapy activity and remarkable combination dose-dependent responses in gastric cancer provides confidence not only for oncology but also for new areas such as autoimmunity. HCB101’s differentiated mechanism and safety profile open the door to rational combinations and next-generation applications well beyond cancer."

About HCB101: A Differentiated CD47-SIPRα Blockade
HCB101 is a 3.5th-generation, affinity-optimized SIRPα-Fc fusion protein with intact IgG4 effector function, developed using HanchorBio’s proprietary FBDB platform. Engineered for selective CD47 blinding on tumors with low affinity for red blood cells, HCB101 avoids the hematologic toxicities commonly associated with anti-CD47 monoclonal antibodies, while preserving strong antibody-dependent cellular phagocytosis (ADCP) and innate-to-adaptive immune bridging.

Key Differentiators of HCB101:

Enhanced safety: Low RBC binding minimizes anemia and thrombocytopenia risk.
Robust immune activation: Engineered to enhance ADCP and innate-to-adaptive bridging.
Broad tumor applicability: Demonstrated activity in >80 PDX/CDX preclinical models.
Clinical translation: Early efficacy as monotherapy with durable disease control, and 100% ORR and disease control rate (DCR) at the middle dose cohort in combination with standard-of-care for 2L-gastric cancer.

(Press release, Hanchor Bio, OCT 23, 2025, View Source;oncology-302592241.html [SID1234656961])

On October 23, 2025 GSK plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) has approved Blenrep (belantamab mafodotin-blmf) in combination with bortezomib and dexamethasone (BVd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory (IMID) agent.

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The Blenrep approval is supported by data from the pivotal DREAMM-7 phase III trial. In patients who had two or more prior lines of therapy (3L+), including a PI and an IMID, Blenrep in combination demonstrated a clinically meaningful 51% reduction in the risk of death [HR 0.49, 95% confidence interval (CI): 0.32-0.76] and a tripled median progression-free survival (PFS) of 31.3 months [95% CI: 23.5-NR)] versus 10.4 months [95% CI: 7.0-13.4] for a daratumumab-based triplet (DVd) [HR 0.31, 95% CI: 0.21-0.47]. The safety and tolerability profiles of the Blenrep combination were broadly consistent with the known profiles of the individual agents.2

Tony Wood, Chief Scientific Officer, GSK, said: "Today’s FDA approval of Blenrep is another significant milestone, providing potential for superior efficacy, including overall survival, to US patients. There is an urgent need for new and novel therapies, as nearly all patients with multiple myeloma experience relapse and re-treating with the same mechanism of action often leads to suboptimal outcomes. As the only anti-BCMA agent that can be administered across healthcare settings, including in community centres where 70% of patients receive care, Blenrep fulfils a major patient need. We believe Blenrep can redefine treatment for patients with multiple myeloma in all parts of the world, and we are accelerating its development in earlier lines of therapy to support its use across all stages of this difficult-to-treat cancer."

Working closely with the FDA, Blenrep is available through a new, streamlined Risk Evaluation and Mitigation Strategy (REMS). The new REMS supports appropriate use and patient safety while reducing administrative burden through simplified patient forms, removal of duplicative checklists and efficient communication between HCPs and either optometrists or ophthalmologists monitoring eye care. GSK will also offer Together with GSK, an optional patient support programme available to all US patients prescribed Blenrep.

Data from the DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical trial programme will be submitted to the National Comprehensive Cancer Network (NCCN) guidelines this year. Recent results from the DREAMM studies, alongside emerging real-world evidence, provide a growing body of data for Blenrep.5,6

Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University in Atlanta, Georgia, Chair of Emory Department of Hematology and Medical Oncology, said: "With the approval of Blenrep, we now have a community-accessible BCMA-targeting agent with the potential to improve outcomes for patients following two or more prior lines of treatment, where options are limited. This approval marks an important advance in the US relapsed/refractory treatment landscape."

Michael Andreini, President and Chief Executive Officer of the Multiple Myeloma Research Foundation and the Multiple Myeloma Research Consortium, said: "The reality for most patients with multiple myeloma is a relentless cycle of remission and relapse, as their disease becomes refractory to treatments. Patients urgently need more effective treatment options that can offer more quality time with their loved ones. We see the potential for Blenrep in combination to help patients achieve this."

GSK is advancing the DREAMM clinical programme to demonstrate Blenrep’s potential benefit in earlier lines of treatment. Follow-up continues for overall survival (OS) in both DREAMM-7 and DREAMM-8 with data expected in early 2028, including in patients who have received only one prior line of therapy. DREAMM-10, a phase III trial in newly diagnosed transplant-ineligible patients, which represent over 70% of patients starting therapy, was initiated in Q4-2024.4 Interim efficacy and safety data for Blenrep as a first line treatment are expected in early 2028 with enrolment expanded to US sites to increase US patient representation in the study population. GSK continues to work with the FDA for US patients.

Approvals outside of the US
Blenrep combinations are approved in 2L+ relapsed or refractory multiple myeloma in the European Union7, UK8, Japan9, Canada, Switzerland and Brazil. Applications are currently under review in other markets globally, including China10 where the application is based on the results of DREAMM-7 and has been granted Breakthrough Therapy Designation and Priority Review.

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.11,12 There are approximately 180,000 new cases of multiple myeloma diagnosed globally each year. Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.13 Many patients with multiple myeloma, including approximately 70% in the US, are treated in a community cancer setting, leaving an urgent need for new, effective therapies with manageable side effects that can be administered outside of an academic centre.3,15,16

About Blenrep
Blenrep is a monoclonal ADC (antibody-drug conjugate) comprising a humanised BCMA (B-cell maturation antigen) conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Indication
In the US, Blenrep is indicated in combination with bortezomib and dexamethasone (BVd) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Please see accompanying US Prescribing Information which will soon be available here17.

About DREAMM-7
DREAMM-7 is a multicentre, open-label, randomised phase III clinical trial evaluating the efficacy and safety of belantamab mafodotin combined with bortezomib plus dexamethasone (BVd) compared to daratumumab combined with bortezomib plus dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy. The trial enrolled 494 participants who were randomised 1:1 to receive either BVd or DVd. Belantamab mafodotin was administered at a dose of 2.5mg/kg intravenously every three weeks in combination for the first eight cycles and then continued as a single agent. The primary endpoint was PFS as per an independent review committee, with secondary endpoints including OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

PFS results17 were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024 and published in the New England Journal of Medicine. OS results18 were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2024.

About DREAMM-10
DREAMM-10 is a multicentre, open-label, randomised phase III clinical trial in newly diagnosed transplant ineligible patients with multiple myeloma, evaluating belantamab mafodotin plus lenalidomide and dexamethasone (BRd) versus daratumumab plus lenalidomide and dexamethasone (DRd).

(Press release, GlaxoSmithKline, OCT 23, 2025, View Source [SID1234656945])

On October 23, 2025 Jacobio Pharma (1167.HK) reported that it presented the pre-clinical data of its internally discovered pan-KRAS inhibitor JAB-23E73 in a poster presentation at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).

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The pre-clinical results demonstrated that JAB-23E73 is a highly potent pan-KRAS (ON/OFF) inhibitor with strong selectivity that spares HRAS and NRAS inhibition. The compound exhibits superior antitumor activity across multiple cancer types harboring different KRAS driver mutations or amplification.

In KRAS-driven mouse tumor models, JAB-23E73 induced tumor regression without causing significant body weight loss, indicating good tolerability and a wide therapeutic window. The compound also showed a favorable pharmacokinetic profile for oral administration and exhibited plasma drug concentration-dependent intratumoral p-ERK inhibition.

Phase I clinical trials of JAB-23E73 are currently ongoing in both China and the United States for patients with advanced solid tumors harboring KRAS gene alterations.

(Press release, Jacobio Pharmaceuticals, OCT 23, 2025, View Source [SID1234656962])

On October 23, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported preclinical data for HMPL-A251 at the AACR (Free AACR Whitepaper)‑NCI‑EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), held October 22–26, 2025, in Boston, USA. HMPL-A251 is a first-in-class PI3K/AKT/mTOR ("PAM")-HER2 Antibody-Targeted Therapy Conjugate ("ATTC") comprising of a highly selective and potent PI3K/PIKK inhibitor payload linked to a humanized anti-HER2 IgG1 antibody, via a cleavable linker.

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HER2 is a well-established therapeutic target. HER2 overexpression is found in a variety of cancer types and often associated with poor prognosis. As a key downstream signaling pathway of HER2, the PAM pathway contributes significantly to the resistance against HER2-targeting treatments when altered. HMPL-A251 is innovatively designed to leverage the synergy between HER2 targeting and PAM pathway inhibition to address limitations of traditional toxin-based antibody-drug conjugates ("ADCs") and standalone PAM inhibitors.

In vitro, the PI3K/PIKK inhibitor payload exhibited high potency, selectivity, and broad anti-tumor activity across a panel of 130 tumor cell lines. By conjugating this potent payload with an anti-HER2 antibody via a hydrophilic linker, the ATTC compound HMPL-A251, upon binding to the HER2-positive target cells, undergoes rapid internalization, lysosomal trafficking, payload release, and inhibition of PAM and PIKK signaling, inducing tumor cell apoptosis. HMPL-A251 demonstrated HER2-dependent antitumor activity in vitro, potently inhibiting HER2-positive tumor cell growth regardless of PAM pathway alterations, with moderately reduced activity in HER2-low, PAM-altered cell lines. HMPL-A251 also demonstrated a bystander effect on HER2-null cells when co-cultured with HER2-positive cells.

Unlike toxin-based ADCs, which often face challenges with toxicity related to their cytotoxic payloads, ATTCs are designed to prioritize tumor-specific delivery of a pathway-modulating payload, enhancing safety for long‑term use and enabling potential frontline combinations with chemotherapy. In vivo, HMPL-A251 demonstrated superior anti-tumor efficacy and tolerability as compared to the naked antibody and payload administered together. A single intravenous dose of HMPL-A251 induced tumor regression across multiple models including HER2-positive and HER2-low models with or without PAM alteration. Efficacy correlated strongly with payload concentration and target inhibition in tumor tissue. Notably, when benchmarked against T-DXd (trastuzumab deruxtecan, a HER2‑directed ADC), HMPL-A251 achieved superior or comparable efficacy at equivalent doses in most tested models. Moreover, payload-based toxicities are expected to be low, as the plasma exposure of free payload was much lower than for HMPL-251, with a mass ratio of less than 1:500,000.

"We are excited to share the progress of HMPL-A251, the first candidate from our ATTC platform. It represents a potentially significant leap forward in addressing the limitations of toxin-based ADCs and narrow therapeutic window of systemic PAM inhibitors. By combining selective PI3K/PIKK inhibition with precise HER2 targeting, HMPL-A251 achieves potent antitumor effects while maintaining a favorable safety profile," said Dr Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED. "The compelling preclinical data presented underscore its potential to redefine treatment for a wide spectrum of cancers, and we are excited to advance HMPL-A251 as well as more ATTC drug candidates toward clinical trials."

HUTCHMED plans to initiate global clinical trials for HMPL-A251 around the end of 2025, followed by multiple global Investigational New Drug (IND) filings for more ATTC candidates in 2026.

About the ATTC platform
HUTCHMED’s Antibody-Targeted Therapy Conjugate platform represents a next-generation approach to precision oncology, combining monoclonal antibodies with proprietary small-molecule inhibitor payloads to deliver dual mechanisms of action. Unlike traditional cytotoxin-based ADCs, ATTCs combine targeted therapies to achieve synergistic anti-tumor activity and durable responses in preclinical models, outperforming standalone antibody or small-molecule inhibitor components in efficacy and safety.

Built on over 20 years of targeted therapy expertise, the platform enables development of drug candidates for diverse cancer types. By leveraging antibody-guided delivery and tumor-specific payload release, ATTCs improve the accessibility to tumors and reduce off-tumor toxicity. This overcomes challenges of traditional small-molecule inhibitors, ensures safer long-term use, and supports combinations with chemotherapy and immunotherapy, unlocking potential for early-line treatments.

(Press release, Hutchison China MediTech, OCT 23, 2025, View Source [SID1234656946])

On October 23, 2025 Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation (BTD) to zenocutuzumab-zbco for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion. The designation was supported by results from the ongoing investigational Phase 2 eNRGy trial. These findings will be presented as both an oral and poster presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, MA and will serve as the basis for a supplemental Biologics License Application (sBLA) that will be submitted to FDA in 2026.

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BTD is granted by the FDA to expedite the development and review of therapies that may demonstrate substantial improvement over existing treatments for serious or life-threatening conditions. The designation conveys all of the fast track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment, and eligibility for rolling review and priority review. For adult patients with advanced unresectable or metastatic NRG1+ cholangiocarcinoma, a rare and aggressive cancer with limited treatment options, this designation underscores the urgent need for effective therapies and recognizes the potential of zenocutuzumab-zbco to help address this significant unmet medical need.

The designation was supported by new interim data presented at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) meeting which evaluated zenocutuzumab-zbco in patients with advanced NRG1+ cholangiocarcinoma in the eNRGy trial. In 19 evaluable patients, the results demonstrated an investigator-assessed overall response rate of 37%, a median duration of response of 7.4 months, and a median time to response of 1.9 months. Progression-free survival was 9.2 months and clinical benefit rate, defined as partial/complete response or stable disease for ≥24 weeks, was 58%. Among patients with evaluable CA 19-9 data, all experienced a decline in serum levels, including a >50% reduction in 69% of patients. The safety profile was consistent with the overall eNRGy trial population, with most adverse events grade 1 or 2. Five patients (23%) experienced serious adverse events, none considered treatment related, and no patients discontinued therapy due to treatment-related toxicity.

Dr. Alison M. Schram, Principal Investigator of the eNRGy trial and medical oncologist from Memorial Sloan Kettering Cancer Center, commented: "NRG1 fusions represent a rare but actionable driver in cholangiocarcinoma, and the data from the eNRGy trial continue to highlight the potential of zenocutuzumab to offer meaningful clinical benefit for these patients. I’m honored to present these findings at AACR (Free AACR Whitepaper)-NCI-EORTC, where we can advance the dialogue around targeted therapies in hard-to-treat cancers."

"Patients with cholangiocarcinoma face an aggressive disease with limited standard therapy options," said Juan W. Valle, MD, Chief Medical Officer of the Cholangiocarcinoma Foundation. "The eNRGy trial results are encouraging, and they underscore how critical comprehensive molecular testing, notably tissue-based RNA NGS, is to ensure that patients with rare drivers such as NRG1 fusions are identified and can potentially have access to targeted treatments."

"In December 2024, zenocutuzumab-zbco (tradename BIZENGRI) received accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The new data from the eNRGy trial highlight the potential of zenocutuzumab-zbco as a promising treatment option for patients with NRG1 fusion–positive cholangiocarcinoma," said Pritesh J. Gandhi, PharmD, Chief Development Officer of Partner Therapeutics. "With the growing number of genomic alternations and gene fusions that are now actionable, it is imperative that oncologists order upfront tissue-based RNA next generation sequencing to ensure that gene fusions, of which NRG1 is just one, are not missed."

A copy of the poster and presentation will be available on the Partner Therapeutics website under the research tab following the conference. Additional meeting information can be found on the AACR (Free AACR Whitepaper)-NCI-EORTC website.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.

Dr. Schram has financial interests related to Partner Therapeutics.

About NRG1 Gene Fusions

NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably tissue-based RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1.

About BIZENGRI (zenocutuzumab-zbco)

INDICATIONS

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

BOXED WARNING: EMBRYO-FETAL TOXICITY

Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.

WARNINGS AND PRECUATIONS

Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions

BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.

Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.

Interstitial Lung Disease/Pneumonitis

BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated.

Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed.

Left Ventricular Dysfunction

BIZENGRI can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.

Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI.

Embryo-Fetal Toxicity

Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.

ADVERSE REACTIONS

NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC

Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).

In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).

NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI.

There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure.

In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).

Please see full Prescribing Information, including Boxed Warning

(Press release, Partner Therapeutics, OCT 23, 2025, View Source [SID1234656963])