tilatamig samrotecan (AZD9592) / AstraZeneca - LARVOL DELTA

EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov) - P1 | N=190 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Aug 2028 ➔ Jun 2026

First-in-human • Monotherapy • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MST01-AZN-05: PBI-MST-01 (NCT04541108) Substudy AZN-05: Intratumoral Microdosing of Rilvegostomig, Volrustomig, Sabestomig, and AZD9592 in HNSCC (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Presage Biosciences | Recruiting ➔ Completed | Trial completion date: Apr 2025 ➔ Mar 2026 | Trial primary completion date: Feb 2025 ➔ Mar 2026

Trial completion • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov) - P1 | N=167 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | N=403 ➔ 167

Enrollment change • Enrollment closed • First-in-human • Monotherapy • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Preclinical data of IBI3028, the first clinical-stage bispecific dual-payload ADC, targeting EGFR/c-MET–positive advanced solid tumors. (ASCO 2026) - "IBI3028 demonstrated superior efficacy to AZD9592 in xenograft models with varying EGFR/c-Met expression levels. IBI3028 demonstrates outstanding preclinical efficacy and safety profile, and is well positioned as a promising broad-spectrum therapeutic for advanced solid tumors with EGFR/c-MET expression or EGFR/c-Met-driven pathogenesis."

ADC • Bispecific • Metastases • Preclinical • Oncology • Solid Tumor • EGFR • MET

Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Presage Biosciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov) - P1 | N=403 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Oct 2027 ➔ Aug 2028 | Trial primary completion date: Oct 2027 ➔ Aug 2028

First-in-human • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Hanjugator camptothecin platform: Effective, low-toxicity design maximizing antibody functionality and delivering potential best-in-class EGFR/cMet bispecific antibody-drug conjugate (AACR 2026) - "In vivo efficacy of EGFR/cMet-LPA003 was tested in multiple xenograft models (LU387, SW48, HT29, NCI-H1975)...Medium-potency LPA003, conjugated to EGFR/cMet bispecific antibody, induced significant tumor regression at single 3 mg/kg doses in various xenograft models, outperforming AZD9592 in the HT29 CDX model... We have developed Hanjugator, a versatile camptothecin-based linker-payload platform with tunable toxin potency. This modular design accommodates diverse targets and ADC programs, optimizing dosing regimens and broadening clinical applications. The LPA003-conjugated EGFR/cMet bispecific ADC exhibits a superior therapeutic index, maximizing antibody-mediated signaling blockade, and positions as best-in-class molecule with Investigational New Drug submission anticipated in Q1 2026."

ADC • Bispecific • Oncology

AZD9592, an EGFR/cMET bispecific antibody-drug conjugate (ADC), demonstrates target-dependent efficacy in colorectal cancer (CRC) patient-derived xenograft (PDX) models (AACR 2025) - "Despite recent advances in ADC development for CRC, such as the use of trastuzumab deruxtecan to treat HER2-positive CRC, a significant unmet need remains for novel therapeutic approaches, particularly for patients with limited targeted treatment options. We evaluated the antitumor efficacy of AZD9592 and explored biomarker-response relationships in CRC PDX models across a range of very low to high EGFR expression (optical density of membrane [OD] 6.7-162.6) and cMET expression (OD 18.5-142.6) measured by immunohistochemistry-quantitative continuous score (IHC-QCS), as well as other molecular features like oncogene drivers. AZD9592 demonstrated dose-dependent antitumor activity in CRC PDX models, including KRAS-mutant and KRAS-wildtype tumors. These responses suggest opportunities for clinical development of AZD9592 in CRC and the potential for biomarker-guided patient selection."

ADC • Bispecific • Clinical • Colorectal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • KRAS • TOP1

KA-2886-LD38: a bispecific antibody-drug conjugate (ADC) targeting both EGFR and MET, incorporating a novel linker-payload that inhibits DNA topoisomerase I (AACR 2025) - "Compared to the benchmark ADC AZD9592, KA-2886-LD38 exhibits a similar internalization rate when binding to tumor cells but demonstrates significantly stronger cytotoxicity and bystander killing activity across different tumor cell lines in vitro...Moreover, KA-2886-LD38, when combined with osimertinib, also demonstrated a combination inhibitory effect on H1975 tumor growth. KA-2886-LD38 is well-tolerated at doses up to 30 mg/kg in EGFR and MET humanized genetically modified mice, and toxicity studies in monkeys are ongoing. These results suggest that KA-2886-LD38 has remarkable potential in the landscape of anti-EGFR/cMet therapies."

ADC • Bispecific • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • EGFR • TOP1

Establishing preclinical activity of topoisomerase I inhibitor (TOPO1i) antibody-drug conjugate AZD9592 in patient-derived xenograft (PDX) models of metastatic colorectal cancer (mCRC) in context of irinotecan pretreatment and resistance (AACR 2025) - "We evaluated these models for aresponse to AZD9592 (administered in a single dose at 2, 4, or 8 mg/kg), irinotecan, or irinotecan plus oxaliplatin. AZD9592 was effective in mCRC PDX models, even at the lowest doses tested. AZD9592 was effective in mCRC PDX models that did not respond to irinotecan-based treatment. Ongoing research is evaluating whether multiple doses of AZD9592 can induce resistance in PDX models, and potential resistance mechanisms are being assessed by molecular characterization."

ADC • Metastases • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • EGFR

VBC101-F11: An innovative EGFR/cMet bispecific antibody drug conjugate (ADC) targeting key oncogenic drivers in solid tumors (AACR 2024) - "This innovative design distinguishes VBC101-F11 from other EGFR/cMet-targeting agents on the market or in clinical trials (ABBV399 or AZD9592), optimizing both efficacy and safety.1. Further payload exploration, such as DNA replication inhibitor, has also yielded promising results, with VBC101-F11-new payload showing comparable efficacy to the same class ADC AZD9592 in models with low EGFR and high cMet expression (100% TGI) and in those with moderate EGFR/cMet expression (~ 60% TGI).In summary, VBC101-F11, with unique design and distinguished attributes, has demonstrated its remarkable potential in the landscape of anti-EGFR/cMet therapies. The encouraging efficacy observed in preclinical models supports the molecule's advancement into clinical development, positioning it as a best-in-class bispecific ADC for treating tumors in patients."

ADC • Bispecific • Late-breaking abstract • Lung Cancer • Oncology • Solid Tumor

Tilatamig samrotecan: Data from P1 EGRET trial (NCT05647122) for advanced solid tumors/NSCLC/HNSCC/CRC in 2027 (AstraZeneca) - FY 2025 Results

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

AZD9592: Data from P1 EGRET trial (NCT05647122) for advanced solid tumors/NSCLC/HNSCC/CRC post 2026 (AstraZeneca) - Q3 2025 Results

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov) - P1 | N=403 | Recruiting | Sponsor: AstraZeneca | N=228 ➔ 403 | Trial completion date: Jan 2026 ➔ Oct 2027 | Trial primary completion date: Jan 2026 ➔ Oct 2027

Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

AZD9592: Data from P1 EGRET trial (NCT05647122) for advanced solid tumors/NSCLC/HNSCC/CRC in H2 2025 (AstraZeneca) - Q1 2025 Results

P1 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov) - P1 | N=228 | Recruiting | Sponsor: AstraZeneca | N=162 ➔ 228

Enrollment change • Monotherapy • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions. (PubMed, Antibodies (Basel)) - " Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody...Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A promising MET-EGFR bispecific nanobody-drug conjugate therapy for multiple solid tumours (ESMO 2024) - "KY-0301 was engineered with lower EGFR affinity (161-fold) and EGFR arm truncation, with the aim of reducing EGFR-driven toxicity in normal tissues. KY-0301 showed higher internalization rates than AZD9592 in HCT116 and NCI-H1975. Preclinical data has demonstrated promising efficacy and safety of KY-0301 in tumors expressing MET and EGFR, including but not limited to NSCLC, colorectal cancer, pancreatic cancer and kidney cancer."

Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • EGFR • MET

AZD9592: Data from P1 EGRET trial (NCT05647122) for advanced solid tumors/NSCLC/HNSCC/CRC in H2 2025 (AstraZeneca) - H1 & Q2 2024 Results

P1 data • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov) - P1 | N=162 | Recruiting | Sponsor: AstraZeneca | N=108 ➔ 162

Combination therapy • Enrollment change • Metastases • Monotherapy • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

EGRET: First in Human Study of AZD9592 in Solid Tumors (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2025 ➔ Oct 2025 | Trial primary completion date: Mar 2025 ➔ Oct 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

AZD9592: Data from P1 EGRET trial (NCT05647122) for advanced solid tumors/NSCLC/HNSCC in 2025 (AstraZeneca) - Q4 & FY2023 Results

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Maximizing Preclinical Data to Tailor Translational Plans for Bispecific ADC: Lessons From AZD9592, an EGFR-cMET Bispecific ADC (ADC-USA 2023) - "Exploring the characterization of internalization and cytotoxic properties of AZD9592, a bispecific ADC designed to selectively bind EGFR and c-MET on tumor cells and deliver a topoisomerase 1 inhibitor payload; Using in vivo PDX studies to explore relationship of target expression to tumor growth inhibition; Describing pharmacodynamic biomarkers supporting multi-faceted mechanism of action"

Preclinical • Oncology • EGFR • MET

In Vivo Efficacy of AZD9592, an EGFR-cMET Bispecific ADC, in a Broad Panel of NSCLC Patient-Derived Xenograft Models (IASLC-WCLC 2023) - "Comparable efficacy was observed across EGFR mutant (EGFRm) models previously treated with single or multiple lines of first- (gefitinib, erlotinib), second- (afatinib), and/or third-generation (osimertinib) EGFR TKIs. Additionally, TR was observed in 3/3 (100%) of models previously treated with an EGFR TKI in combination with the cMET TKI savolitinib; high cMET expression by IHC was seen in >90% of the cells in these three models. Notably, 4/5 (80%) of models with prior exposure to the ALK TKI crizotinib demonstrated TR... In vivo efficacy of AZD9592 was demonstrated in PDX models across a broad spectrum of NSCLC molecular profiles. These included EGFRwt and EGFRm tumours harbouring varied EGFR mutations; groups with and without prior chemotherapy; and groups with and without prior treatment with ALK, EGFR, and/or cMET TKI. These observations suggest that AZD9592 may provide clinical benefit in areas of unmet need, including in patients previously treated with..."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

EGRET: First-in-human Study of the Novel Antibody-drug Conjugate AZD9592 ± Anti-cancer Agents in Advanced Solid Tumours (IASLC-WCLC 2023) - P1 | "Module 2 will evaluate AZD9592 in combination with osimertinib in patients with EGFRm mNSCLC. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting."

Metastases • P1 data • Cardiovascular • Head and Neck Cancer • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • TOP1