Margenza (margetuximab-cmkb) / MacroGenics, GC Biopharma, ZAI Lab, TerSera Therap - LARVOL DELTA

The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial. (PubMed, Nat Med) - P1 | "Primary endpoints were safety and maximum tolerated dose of tebotelimab when administered as a single agent (n=269) or in combination with the anti-HER2 antibody margetuximab (n=84). The confirmed objective response rate in these patients was 19% (14/72), including responses in patients typically not responsive to anti-HER2/anti-PD-1 combination therapy. ClinicalTrials.gov identifier: NCT03219268 ."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • LAG3

Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A. (PubMed, ESMO Open) - "The chemotherapy-free regimen of combined margetuximab/retifanlimab as first-line treatment in double biomarker-selected patients demonstrated a favorable toxicity profile compared with historical outcomes using chemotherapy plus trastuzumab. The ORR observed in this study compares favorably versus ORR observed with other chemotherapy-free approaches."

IO biomarker • Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • HER-2 • MSI

Circulating Tumor DNA as a Predictive Biomarker for Clinical Outcomes With Margetuximab and Pembrolizumab in Pretreated HER2-Positive Gastric/ Gastroesophageal Adenocarcinoma. (PubMed, Oncology (Williston Park)) - P1b/2 | "Current ERBB2 status may be more effective than archival status at predicting clinical benefit from margetuximab plus pembrolizumab therapy. ctDNA testing for ERBB2 status prior to treatment will spare patients from repeat tissue biopsies, which may be reserved for reflex testing when ctDNA is not detected."

Biomarker • Circulating tumor DNA • Clinical data • IO biomarker • Journal • Retrospective data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial. (PubMed, J Clin Oncol) - P3 | "Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted."

Journal • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • FCGR3A • HER-2

A prospective, single-arm, multicenter exploration of the treatment of EGFR-positive, unresectable, recurrent or metastatic squamous cell carcinoma of the urogenital system (urethra, penis, kidney, ureter, bladder, etc.) with at least one line of systemic chemotherapy using durvalumab (EGFR-ADC) in combination with pembrolizumab (PD-1) (ChiCTR) - P=N/A | N=28 | Not yet recruiting | Sponsor: Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

New trial • Oncology • Squamous Cell Carcinoma • Urology • EGFR

MARGOT/TBCRC052: A randomized phase II trial comparing neoadjuvant paclitaxel/margetuximab/pertuzumab (TMP) vs paclitaxel/trastuzumab/pertuzumab (THP) in patients (pts) with stage II-III HER2+ breast cancer. (SABCS 2024) - "There was no statistically significant improvement in pCR rate with neoadjuvant TMP vs THP for pts with HER2+ EBC and CD16A FF/ FV genotype. Safety and tolerability were similar between the two regimens, aside from increased rates of infusion-related reactions and alopecia in the margetuximab arm (scalp-cooling use was not recorded). Given numerical improvement in pCR rate, comparative analysis of immune activation biomarkers between the two tx arms will be performed."

Clinical • Late-breaking abstract • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • FCGR3A • HER-2

Peripheral immune profiling during neoadjuvant HER2-targeted therapy in HER2-positive (HER2+) early breast cancer (EBC): Mass cytometry (CyTOF) analysis from the MARGOT trial (SABCS 2025) - P2 | " The investigator-initiated MARGOT trial (NCT04425018/TBCRC052) randomized 171 patients with stage II-III HER2+ EBC 1:2 to receive neoadjuvant THP (trastuzumab/pertuzumab/paclitaxel) or TMP (margetuximab/pertuzumab/paclitaxel). Neoadjuvant chemotherapy plus anti-HER2 therapy induces early changes in circulating immune populations in HER2+ EBC. PBMC profiling reveals a rapid decline in circulating monocytes and NK cell subsets after 3 weeks of therapy, potentially reflecting tumor migration and contribution to ADCC."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD8

Efficacy evaluation of novel targeted drugs in patients with human epidermal growth factor receptor 2-positive breast cancer: A meta-analysis based on multiple sets of clinical data. (PubMed, J Int Med Res) - "Participants were adult females diagnosed with human epidermal growth factor receptor 2-positive breast cancer who were treated with novel agents (e.g. T-DXd, margetuximab, and tucatinib). Furthermore, novel drugs were associated with lower incidences of cardiotoxicity (5% vs. 15%) and gastrointestinal reactions (10% vs. 25%).ConclusionsNovel targeted drugs demonstrate superior efficacy and a more favorable safety profile than traditional therapies in patients with human epidermal growth factor receptor 2-positive breast cancer. These findings provide a clinical basis for optimizing individualized treatment, particularly for high-risk subgroups."

Clinical data • Journal • Retrospective data • Breast Cancer • Cardiovascular • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • HER-2

Gut Microbiome (GM) characteristics and association with pathologic complete response (pCR) in patients with Breast Cancer treated with neoadjuvant therapy (ESMO-BC 2026) - P2 | "Species- and pathway-level associations were evaluated using MaAsLin3 with false discovery rate correction. We included 43 patients with HER2-positive breast cancer (38 treated with TMP (paclitaxel, margetuximab, pertuzumab), 15 with THP (paclitaxel, trastuzumab, pertuzumab); 31 with RCB 0/I and 12 with RCB II/III) and 37 patients with TNBC, of whom 32 received chemo-immunotherapy, 5. Baseline GM diversity and composition were not associated with RCB in this cohort. Lower RCB was associated with a higher abundance of a thioredoxin-related functional pathway. Suggesting that microbial redox-related activity, potentially impacting T-cell function and reflected in thioredoxin levels, may be more relevant to treatment response than overall microbiome composition, and warrants further investigation."

Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • TXN

Decoding the Genetic Hallmarks of Breast Cancer: Molecular Signatures, Prognostic and Therapeutic Perspectives. (PubMed, Appl Biochem Biotechnol) - "Current FDA approved drugs and drugs in clinical trials targeted toward the genetic influences of breast cancer include those such as Talazoparib and Margetuximab. Additionally, risk assessment and genetic screening methods are incredibly important to inform patients of their individual risk for breast cancer development. Advancements in understanding of gene specific mechanism and their correlation with breast cancer pathogenesis may provide efficient strategies for precision medicine and enhancing clinical outcomes in breast cancer patients."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CHEK2 • HER-2 • PALB2

Long-term cardiotoxicity outcomes of trastuzumab and cardiac safety of novel HER2-targeted therapies. (PubMed, Expert Opin Drug Saf) - "Available evidence suggests that trastuzumab-related cardiotoxicity remains clinically relevant, whereas newer HER2-targeted agents generally demonstrate favorable cardiac safety profiles with mostly asymptomatic and reversible events. These findings support individualized, risk-adapted cardiac monitoring strategies to balance oncologic efficacy with cardiovascular safety."

Clinical • Journal • Review • Breast Cancer • Cardiovascular • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Development of novel NCG-hIL15 and hIL-2 mouse models for preclinical assessment of human NK cell function (AACR 2026) - "The NCG-hIL2 model proved highly effective for assessing ADCC-mediated antibodies such as Trastuzumab, Margetuximab, Rituximab, and Blinatumomab. Together, the NCG-hIL2 and NCG-hIL15 models provide powerful and complementary platforms for studying human NK cell biology, cytokine-driven immunity, and anticancer immunotherapy."

Preclinical • Oncology • IL15 • IL2

Development and application of the NCG-hIL2 mouse model: A humanized platform for enhanced NK cell evaluation in ADCC efficacy testing (AACR 2024) - "Moreover, we demonstrate its utility in the evaluation of therapeutic antibodies, specifically Trastuzumab and the ADCC-enhanced Margetuximab, in the context of ADCC efficacy testing. By reconstituting human NK cells and leveraging the role of IL2, this model offers an enhanced platform for preclinical evaluation of therapeutic antibodies, ultimately advancing our ability to harness NK cell-mediated antitumor responses. It is poised to contribute significantly to the field of cancer immunotherapy and drug development."

ADC • Preclinical • Oncology • IL2

Patient-derived xenograft (PDX) models with differential HER2 expression for preclinical evaluation of HER2-targeted therapies (AACR 2024) - "These models were subsequently treated with HER2-targeted drugs, including Trastuzumab (Herceptin), Margetuximab, and Enhertu.Our results demonstrated differential drug responses corresponding to the varying HER2 expression levels in the PDX samples. This underscores the significance of selecting the right therapeutic approach based on the HER2 status of individual patient.Our collection of PDX models with differential HER2 expression levels provides a robust platform for preclinical evaluation of HER2-targeted therapies. This approach not only addresses the clinical challenge of HER2 heterogeneity but also facilitates a more personalized and effective treatment strategy for gastric cancer patients."

Preclinical • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Efficacy and safety of retifanlimab in gastrointestinal malignancies: A systematic review of clinical trials. (ASCO-GI 2026) - "Background: Retifanlimab is a humanized anti–PD-1 monoclonal antibody, recently approved in May 2025, for advanced squamous cell carcinoma of the anal canal (SCAC) as monotherapy or in combination with carboplatin and paclitaxel...In HER2-positive, PD-L1-positive, advanced gastric/gastroesophageal adenocarcinoma (GEA), the Single-arm Phase II MAHOGANY Cohort A (n=43) reported ORR 53% and median DOR 10.3 months for first-line retifanlimab plus margetuximab, with 18.6% grade 3 treatment-related AEs and no grade 4–5 events... Retifanlimab demonstrates clinically meaningful efficacy in certain GI malignancies, especially SCAC. Its benefit in biomarker-selected gastric/GEA cancer is promising, whereas evidence in colorectal and pancreatic cancer remains limited. Retifanlimab's efficacy and safety profile is comparable to other PD-1 inhibitors; however, further research is needed to define its role across GI cancers."

Clinical • IO biomarker • Review • Anal Carcinoma • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • HER-2 • PD-L1

Real-world treatment patterns and outcomes in patients with HER2+ metastatic breast cancer after treatment with trastuzumab deruxtecan (T-DXd) in the US (SABCS 2025) - "The most common regimens received as the index LOT were trastuzumab + tucatinib + chemotherapy (TTC; 34.2%), other anti-HER2 (18.9%), trastuzumab + chemotherapy (12.7%), other (12.7%), margetuximab + chemotherapy (8.8%), trastuzumab emtansine (T-DM1; 6.6%), and anti-HER2 TKI + chemotherapy (6.1%). Treatment sequencing data suggest that TTC and other anti-HER2 therapies are being used in the post-T-DXd rw setting, though potential differences by line exist. This study demonstrates an ongoing and substantial unmet need for more effective treatments among patients with HER2+ mBC previously treated with T-DXd, as shown by the short rwPFS/OS and short times on subsequent treatments following T-DXd."

Clinical • HEOR • Metastases • Real-world • Real-world evidence • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

MODULE 4: Selection and Sequencing of Therapy for Relapsed/Refractory HER2-Positive mBC in the Absence of CNS Involvement (SABCS 2025) - "Sponsored by AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Puma Biotechnology Inc. Clinical, biological and practical factors influencing the selection and sequencing of therapy for patients with R/R HER2-positive mBC in the absence of CNS metastases Outcomes documented among patients with previously treated HER2-positive mBC without CNS involvement in pivotal clinical research studies of T-DXd and tucatinib-based combinations Long-term findings with and optimal integration of other evidence-based treatment options, such as neratinib/capecitabine, margetuximab/chemotherapy and T-DM1, into the care of patients with progressive HER2-positive mBC Other promising agents and strategies under investigation for advanced HER2-positive breast cancer Frequency of HER2 mutations in patients with mBC; published findings with neratinib-based therapy for this population"

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Solid Tumor • HER-2

Development of mouse models for preclinical evaluation of cancer mRNA vaccines (SITC 2025) - "Importantly, the NCG-hIL15 model supports robust co-engraftment of both human T and NK cells, establishing its unique value for comprehensive evaluation of immunotherapeutic agents targeting both adaptive and innate immune responses.We further validated the NCG-hIL2, NCG-hIL15 models for preclinical immunotherapy assessment, demonstrating NCG-hIL2 model's utility in evaluating ADCC antibodies like Trastuzumab, Margetuximab, Rituximab and Blinatumomab. Collectively, the NCG-hIL2 and NCG-hIL15 models offer powerful tools for investigating NK cell biology, cytokine-driven development, and immunotherapy evaluation.Conclusions By leveraging humanized cytokine signaling, these systems bridge translational gaps in preclinical research, enabling refined assessment of NK cell-targeted therapies."

Preclinical • Oncology • IL15 • IL2

Lower Incidence of Pancreatic Cancer in Patients on HER2-Targeted Therapy: Potential Implications in Pancreatic Cancer Prevention (ACG 2025) - "Cohort 1 comprised patients who received HER2-targeted agents (trastuzumab, pertuzumab, margetuximab, neratinib, lapatinib, tucatinib, trastuzumab deruxtecan); Cohort 2 included patients with a cancer diagnosis but no exposure to HER2-targeted agents. After matching, 54,338 patients were included in each cohort. The incidence of PC was lower in the HER2-targeted group compared to the control group (276 vs. 329)."

Clinical • Addiction (Opioid and Alcohol) • Bladder Cancer • Diabetes • Gastric Cancer • Genetic Disorders • Hepatology • HER2 Positive Breast Cancer • Metabolic Disorders • Nicotine Addiction • Non Small Cell Lung Cancer • Obesity • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatitis • Solid Tumor

The impact of ethnicity on benefit from novel drugs approved for breast cancer treatment: a systematic review and meta-analysis of randomized phase 3 trials of the last decade. (SABCS 2024) - "23 phase III RCTs were identified in the aBC setting, with 1547 (11.1%) patients of Asian ethnicity. Experimental drugs tested included CDK4/6i (palbociclib, ribociclib, abemaciclib), SERD (elacestrant), PI3Ki (alpelisib), PARPi (olaparib, talazoparib), broad variety of anti-HER2 drugs (tucatinib, trastuzumab deruxtecan, pertuzumab, T-DM1, neratinib, margetuximab), anti-PD-1 and anti-PD-L1 drugs (pembrolizumab, atezolizumab) and anti-TROP2 drug (sacituzumab govitecan). 16 RCTs provided HR (95%CI) for PFS in the subgroup of Asians and 17 RCTs for Non-Asians."

IO biomarker • P3 data • Retrospective data • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

MAHOGANY: Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer (clinicaltrials.gov) - P2/3 | N=82 | Completed | Sponsor: MacroGenics | Active, not recruiting ➔ Completed

Trial completion • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • PD-L1

Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer (clinicaltrials.gov) - P1/2 | N=95 | Completed | Sponsor: MacroGenics | Phase classification: P1b/2 ➔ P1/2

Phase classification • Esophageal Cancer • Gastric Cancer • Oncology • Solid Tumor • HER-2

Monoclonal Antibodies in Metastatic Gastro-Esophageal Cancers: An Overview of the Latest Therapeutic Advances. (PubMed, Int J Mol Sci) - "Combination treatments and new molecules have changed the face of the disease, while more therapies are getting approved on a daily basis. This review aims to analyse the major up-to-date clinical trials using mAbs and immunotherapy for the treatment of advanced gastro-esophageal cancers."

Journal • Review • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor

Complete response with Alpelisib and Trastuzumab in a patient with ER/PR-negative, HER2-positive refractory metastatic breast cancer (SABCS 2024) - "Introduction: Metastatic HER2-positive breast cancer is treated with regimens such as taxane with trastuzumab and pertuzumab followed by trastuzumab deruxtecan (T-DXd). The third line options are ado-trastuzumab emtansine (T-DM1), tucatinib with capecitabine, and trastuzumab...Alpelisib is an oral, α-specific PI3K inhibitor that is approved in combination with fulvestrant in hormone receptor positive, HER2-negative, PIK3CA-mutated advanced breast cancer following progression on or after endocrine therapy...Since 2018, right axillary nodal and chest wall metastases progressed on several lines of systemic therapy including lapatinib and capecitabine, trastuzumab and paclitaxel, trastuzumab and vinorelbine, fam-trastuzumab-deruxtecan-nhki (Enhertu), T-DM1, margetuximab with eribulin, and finally trastuzumab with capecitabine... Alpelisib and trastuzumab can be a viable treatment option for patients with HER2-positive and PIK3CA-mutated metastatic breast cancer. Our case..."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR • PIK3CA

Safety and Preliminary Efficacy of Tucatinib and Alpelisib in Patients with HER2-positive PIK3CA-Mutated Metastatic Breast Cancer (SABCS 2024) - P1/2 | "Treatment consists of twice-daily tucatinib and daily alpelisib at prespecified dose level (DL) with concurrent fulvestrant for hormone receptor-positive cases...Prior HER2-targeted therapies included trastuzumab and pertuzumab (8 patients), T-DM1 (5 patients), tucatinib (4 patients), T-DXd (4 patients), and margetuximab (1 patient)... The combination of tucatinib and alpelisib is tolerable at DL1 and shows remarkable antitumor activity with partial responses in 3 out of 5 evaluable patients (60% overall response rate), including responses in patients treated with prior tucatinib and TDXd. Enrollment continues at DL1. Updated safety and efficacy findings will be presented at SABCS 2024 conference."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA