losatuxizumab vedotin (ABBV-221) / AbbVie - LARVOL DELTA

Bystander effects, pharmacokinetics, and linker-payload stability of EGFR-targeting antibody-drug conjugates Losatuxizumab vedotin and Depatux-M in glioblastoma models. (PubMed, Clin Cancer Res) - "EGFR-targeting ADCs are promising therapeutic options for GBM when delivered intra-tumorally by CED. However, the linker and payload for the ADC must be carefully considered to maximize the therapeutic window."

Journal • PK/PD data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD68

Efficacy and pharmacokinetics of EGFR-targeted antibody-drug conjugates following convection-enhanced delivery in mice with glioblastoma xenografts (AACR-NCI-EORTC 2022) - "CED of either Depatux-M or ABBV-221 can extend survival in EGFR amplified GBM PDXs. However, high concentrations of ABBV-221 are associated with increased neuronal cell loss and toxicity as compared to Depatux-M, suggesting a broader therapeutic window for the latter ADC. Median survival, daysTreatmentGBM6GBM39GBM108AB095 – CED 4920NRAB095-MMAF – CED >80 58 18.5 Depatux-M – IP 57 68 NR Depatux-M – CED >80 >100 NR AB095-MMAE – CED 57 19 NR ABBV-221 – IP 53 >100 NR ABBV-221 – CED >80 >100 NR No"

PK/PD data • Preclinical • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

ABT-806-derived antibody-drug conjugates (ADCs) inhibit growth of malignant mesothelioma in vivo (AACR 2018) - "In-vivo therapeutic studies using the biphasic mesothelioma cell line (MSTO-211H) were conducted with treatment groups involving ABT-414, ABBV-221, ADC control, cisplatin chemotherapy. ABT-806 ADCs show potent anti-tumour activity in MM model, and warrant further exploration as a potential therapy for MM."

IO Biomarker • Preclinical • Mesothelioma

A phase 1 study evaluating safety and pharmacokinetics of losatuxizumab vedotin (ABBV-221), an anti-EGFR antibody-drug conjugate carrying monomethyl auristatin E, in patients with solid tumors likely to overexpress EGFR. (PubMed, Invest New Drugs) - "The high frequency of infusion reactions necessitated early closure of this trial. The detailed mitigation strategies used in this protocol for infusion-related reactions may provide beneficial information for trial design of agents with high infusion reaction rates."

Clinical • Journal • P1 data • PK/PD data • Brain Cancer • Fatigue • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. (PubMed, Pharmaceuticals (Basel)) - "MAb806-derived antibody drug conjugates (ADCs), ABT-414, ABBV-221 and ABBV-322, may represent a novel therapeutic strategy in MM. We demonstrated the specific targeting of the mAb806 epitope expressing MM tumors using Zr-based PET imaging. Our data suggest that targeting EGFR in MM using specific ADCs is a valid therapeutic strategy and supports further investigation of the mAb806 epitope expression as a predictive biomarker."

Clinical • Journal • Lung Cancer • Mesothelioma • Oncology • Solid Tumor

Targeting Multiple EGFR Expressing Tumors with a Highly Potent Tumor-Selective Antibody Drug Conjugate. (PubMed, Mol Cancer Ther) - "ABBV-321 follows the development of related EGFR targeted ADCs including depatuxizumab mafodotin (depatux-m, ABT-414), ABT-806 conjugated to monomethyl auristatin F (MMAF), and ABBV-221 (losatuxizumab vedotin), AM1 antibody conjugated to monomethyl auristatin E (MMAE). Collectively, these data suggest that ABBV-321 may offer an extended breadth of efficacy relative to other EGFR ADCs while extending utility to multiple EGFR-expressing tumor indications. Despite its highly potent PBD dimer payload, the tumor selectivity of ABBV-321 - coupled with its pharmacology, toxicology and pharmacokinetic profiles - support continuation of ongoing Phase 1 clinical trials in patients with advanced EGFR-expressing malignancies."

Journal • Glioblastoma • Head and Neck Cancer • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • EGFR

A Study Evaluating Safety and Pharmacokinetics of ABBV-221 in Subjects With Advanced Solid Tumor Types Likely to Exhibit Elevated Levels of Epidermal Growth Factor Receptor (clinicaltrials.gov) - P1; N=45; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; N=90 ➔ 45

Enrollment change • Enrollment closed • Biosimilar • Colorectal Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Characterization of ABBV-221, a Tumor-Selective EGFR Targeting Antibody Drug Conjugate. (PubMed, Mol Cancer Ther) - "ABBV-221 has similar activity as depatux-m against an EGFR-amplified GBM patient derived xenograft (PDX) model and is highly effective alone and in combination with standard-of-care temozolomide in an EGFRvIII-positive GBM xenograft model. ABBV-221 has similar activity as depatux-m against an EGFR amplified GBM PDX model and is highly effective alone and in combination with standard of care (SOC) temozolomide in an EGFRvIII positive GBM xenograft model. Based on these results, ABBV-221 has advanced to a phase 1 clinical trial in patients with advanced solid tumors associated with elevated levels of EGFR."

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