serclutamab talirine (ABBV-321) / AbbVie - LARVOL DELTA

Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: Safety, pharmacokinetics, and antitumor activity in advanced glioblastoma. (PubMed, Neurooncol Adv) - P1 | "Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. Ser-T monotherapy at doses up to 50 μg/kg initial dose, followed by 25 μg/kg Q4W demonstrated a tolerable safety profile with minimal antitumor activity observed in patients with glioblastoma. The glioblastoma dose-expansion cohort was closed due to a lack of efficacy (NCT03234712)."

Journal • Metastases • P1 data • PK/PD data • Brain Cancer • CNS Tumor • Dermatology • Fatigue • Glioblastoma • Oncology • Pruritus • Solid Tumor • EGFR

Convection enhanced delivery of EGFR targeting antibody-drug conjugates Serclutamab talirine and Depatux-M in glioblastoma patient-derived xenografts. (PubMed, Neurooncol Adv) - "CED of Depatux-M is well tolerated and results in extended survival in orthotopic GBM PDXs. In contrast, CED of Ser-T was associated with a much narrower therapeutic window."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • GFAP

Convection enhanced delivery of EGFR-targeting antibody drug conjugates ABBV-321 and Depatux-M (AACR 2022) - "Depatux-M is well tolerated when infused into normal brain and results in extended survival in orthotopic GBM PDXs. In contrast, ABBV-321, with a distinct PBD toxin, had a much narrower therapeutic window when delivered by CED."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD68 • GFAP

[VIRTUAL] A Phase I Efficacy & Safety Study of Serclutamab Talirine, an EGFR Targeting Antibody Drug Conjugate, in Subjects with Recurrent Glioblastoma (GBM) (ADC-USA 2021) - "Review of targeting EGFR with antibody drug conjugates in solid tumors Examine the efficacy and safety of Serclutamab Talirine in subjects with recurrent glioblastoma Discuss conclusions and future directions"

Clinical • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

[VIRTUAL] Phase I study of the antibody-drug conjugate ABBV-321 in patients with non-small cell lung cancer and squamous head and neck cancer with overexpression of the epidermal growth factor receptor. (ASCO 2020) - P1 | "The dose-escalation phase has been completed; screening and enrollment for the expansion phase of the study in NSCLC and HNSCC is underway. Research Funding: AbbVie, Inc."

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

[VIRTUAL] An investigation into the impact of next generation sequencing on the use of targeted treatments in glioblastoma. (ASCO 2021) - "We excluded cytotoxic chemotherapy agents and bevacizumab as these therapies are utilized regardless of a targeted gene indication...97 patients had EGFR copy number gains or EGFR gain of function mutations of which 21 were treated with depatuxizumab mafodotin, and one additional patient who was treated with ABBV 321...Of these 11, 4 received targeted regimens (36.4%) with either TAS-120, pemigatinib, erdafitinib, or erdafitinib with ponatinib... These preliminary results suggest that NGS data currently does not frequently impact treatment decisions for glioblastoma . Although this study is limited by being a single institution study, future efforts include expanding this analysis to multiple institutions . With improvements in therapeutics as well as with wider availability of NGS testing, sequencing data may impact a larger percentage of glioblastoma patients."

Biomarker • Next-generation sequencing • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EGFR • FGFR3 • TACC3

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=62; Completed; Sponsor: AbbVie; Active, not recruiting ➔ Completed

Clinical • Trial completion • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=80; Recruiting; Sponsor: AbbVie; Trial completion date: Mar 2024 ➔ Oct 2022

Clinical • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=80; Recruiting; Sponsor: AbbVie; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=80; Not yet recruiting; Sponsor: AbbVie

Clinical • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: AbbVie; N=80 ➔ 120; Trial primary completion date: Mar 2019 ➔ Sep 2019

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

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: AbbVie; Trial completion date: Oct 2022 ➔ Jun 2023; Trial primary completion date: Sep 2019 ➔ Mar 2019

Clinical • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: AbbVie; Trial primary completion date: Mar 2019 ➔ Sep 2019

Clinical • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: AbbVie; Trial primary completion date: Sep 2019 ➔ Aug 2021

Clinical • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: AbbVie; Trial completion date: Jan 2023 ➔ May 2021; Trial primary completion date: Jan 2023 ➔ May 2021

Clinical • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: AbbVie; Trial completion date: Aug 2023 ➔ Sep 2025; Trial primary completion date: Aug 2021 ➔ Mar 2024

Clinical • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=62; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; N=120 ➔ 62

Clinical • Enrollment change • Enrollment closed • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • EGFR

A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR) (clinicaltrials.gov) - P1; N=120; Recruiting; Sponsor: AbbVie; Trial completion date: Sep 2025 ➔ Jan 2023; Trial primary completion date: Mar 2024 ➔ Jan 2023

Clinical • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • EGFR

Navitoclax enhances the effectiveness of EGFR-targeted antibody-drug conjugates in PDX models of EGFR-expressing triple-negative breast cancer. (PubMed, Breast Cancer Res) - "The dramatic tumor regressions achieved using combined agents in pre-clinical TNBC models underscore the abilities of BCL-2/X antagonists to enhance the effectiveness of EGFR-targeted ADCs and highlight the clinical potential for usage of such targeted ADCs to alleviate toxicities associated with combinations of BCL-2/X inhibitors and systemic chemotherapies."

IO Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

Pre-clinical assessment of combined ABT-263/Navitoclax and ABT-414 or ABBV-321 treatment for EGFR-expressingTNBC (SABCS 2019) - "Tumor specific EGFR-targeted antibodies (ABT-806) and their antibody-drug conjugates (ADC:414;321), which eliminate side effects associated with systemic anti-EGFR treatments, represent promising alternative therapeutic approaches. Notably, this strategy avoids the toxicities associated with systemic chemotherapy and BCL-2/XL -inhibitors. These results also highlight the translational relevance of 321+263, within the context of EGFR-expressing TNBC."

IO Biomarker • BCL2 • EGFR

ABT-806 Derived Antibody Drug Conjugates (ADCs) Inhibit Growth of Malignant Mesothelioma In-Vivo (IASLC-WCLC 2019) - "...We present data in MM using ABT-806 novel ADCs [ABT-414 (ABT-806- monomethyl auristatin F), ABBV-221 (ABT-806- monomethyl auristatin E), ABBV-322 (ABT-806- pyrrolobenzodiazepine)] and ABBV-321 (Affinity-matured ABT-806- pyrrolobenzodiazepine) in MM patient derived xenografts (PDX)...PDXs were implanted into 5 to 10 NOD-Scid mice per group and treated with control ADC, saline, cisplatin or ABT-806 ADCs and followed longitudinally with caliper measurements... In a disease with limited therapies, ABT-806 targeting ADCs in MM demonstrated significant responses in 806+ PDX and cell lines. These data support clinical expansion of these compounds in 806+ MM patients."

Preclinical

ABT-806 derived antibody drug conjugates (ADCs) inhibit growth of malignant mesothelioma in-vivo. (ASCO 2019) - "...PDXs were implanted into 5 to 10 NOD-Scid mice per group and treated with control ADC, saline, cisplatin or ABT-806 ADCs and followed longitudinally with caliper measurements...In the 806 IHC negative PDX model, the differences in tumor volumes between all groups were found to be non-statistically significant (ADC control vs ABT-414, ADC control vs ABBV-221, ADC-control vs ABBV-321 groups) with p = 0.0597 for one-way ANOVA... In a disease with limited therapies, ABT-806 targeting ADCs in MM demonstrated significant responses in 806+ PDX and cell lines. These data support clinical expansion of these compounds in 806+ MM patients."

Preclinical