ABBV-011 / AbbVie - LARVOL DELTA

Detection of SEZ6, a therapeutic target, in medullary thyroid carcinoma. (PubMed, J Clin Endocrinol Metab) - "SEZ6 may serve as a novel biomarker for MTCs. Although SEZ6 lacks any prognostic values in MTC, its positivity in 91% to 93% of MTCs, including MTCs without RET and RAS mutations, renders SEZ6-targetted antibody-drug conjugate therapy a promising targeted therapy for MTCs."

Journal • CNS Disorders • Endocrine Cancer • Epilepsy • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • SEZ6

A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6-Targeting Antibody-Drug Conjugate, in Patients With Small Cell Lung Cancer. (PubMed, Clin Cancer Res) - P1 | "ABBV-011 1.0 mg/kg Q3W monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation."

Journal • P1 data • CNS Disorders • Epilepsy • Fatigue • Hematological Disorders • Hepatology • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • SEZ6

Development of the enabling route to the ABB-011 drug-linker (ACS-Fall 2024) - "ABBV-011 is an antibody-drug conjugate (ADC) that is comprised of a calicheamicin derived drug-linker 1 that contains a maleimide linker with a cleavable disulfide bond and an engineered monoclonal antibody (mAb)...Namely, each step of the original route required either flash column (FCC) or high-pressure liquid chromatography (HPLC). Additionally, the overall yield of the process was only 7.4%.With these factors in mind, a more convergent route starting from the lower cost N-H-calicheamicin (7) was envisioned which would reduce the amount of potent steps as well as lower the burden on chromatography.The enabling route led to a highly pure drug linker increasing the overall yield to 49% (6.6 fold improvement)."

Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Antibody-drug conjugates treatment of small cell lung cancer: advances in clinical research. (PubMed, Discov Oncol) - "Although toxicities exceeding expectations have been observed with Rova-T, drugs targeting TROP-2 (Sacituzumab Govitecan), B7-H3 (DS-7300), and SEZ6 (ABBV-011) have shown exciting clinical benefits. In this review, we collect the latest clinical evidence to describe the therapeutic efficacy and safety of ADCs in SCLC and discuss prospects and challenges."

Journal • Review • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3 • NCAM1 • SEZ6

ABBV-706 is a novel SEZ6-targeted topoisomerase 1 inhibitor ADC for SCLC and other neuroendocrine cancers (AACR 2024) - P1 | "Furthermore, Top1i inhibition is an effective mechanism of action in SCLC with topotecan approved in 2L, although significant toxicity limits broad utility. As such, we hypothesized that a SEZ6-Top1i ADC would enable effective Top1 inhibition in tumor cells and reduce toxicity relative to ABBV-011 or systemic chemotherapy, driving increased therapeutic benefit...In addition, ABBV-706 had activity in the setting of resistance to cisplatin/etoposide (1L SoC in SCLC), in combination with cisplatin, and in SEZ6-expressing neuroendocrine liver and cervical PDX models...ABBV-706 shows promise as an agent for the treatment of SCLC and other difficult to treat SEZ6 expressing neuroendocrine tumors. ABBV-706 has completed dose escalation, and dose expansion is currently ongoing in a Phase 1 FIH clinical study (NCT05599984)."

Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SEZ6 • TOP1

A Study of ABBV-011 Alone and in Combination With Budigalimab (ABBV-181) in Participants With Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=132 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SEZ6

Preclinical Characterization of Catabolic Pathways and Metabolism of ABBV-011, a Novel Calicheamicin-Based SEZ6 Targeting Antibody Drug Conjugate. (PubMed, Drug Metab Dispos) - "Significance Statement Several in vitro and in vivo stability studies of ABBV-011, a calicheamicin-based ADC, identified circulating metabolites and catabolites and suggested that disulfide cleavage may be a key liability for the conjugated linker-payload. These observations may be relevant to other disulfide-linked ADCs, such as Mylotarg and Besponsa, both of which have reported similar half-lives that possibly indicate instability."

Journal • Preclinical • Developmental Disorders • Lung Cancer • Metabolic Disorders • Oncology • Small Cell Lung Cancer • Solid Tumor • SEZ6

Safety, Tolerability and Pharmacokinetic Study of SC1011 in Healthy Subjects (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Guangzhou JOYO Pharma Co., Ltd

New P1 trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

SC1011 Twice Daily vs Placebo in Patients Diagnosed With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P2/3 | N=210 | Recruiting | Sponsor: Guangzhou JOYO Pharma Co., Ltd

New P2/3 trial • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Antibody-Drug Conjugates Represent Key Area of Focus in Lung Cancer Research (Oncology Nursing News) - "In a panel discussion following the talk, panelists expressed their concern around a lack of understanding behind the mechanism of the unique AEs seen with ADCs. One contributing factor, Narjust Florez, MD...noted was that the bystander effect in lung cancer might be more negative or severe than has been seen in other types of cancer, like breast cancer. 'In the case of lung cancer, the surrounding tissue is different and perhaps more sensitive,' she postulated. 'This is the most exciting area, there are lots of agents, lots of new trials that are ongoing in patients,' said Karen Reckamp, MD...said. 'We need to increase our knowledge of these ADCs to improve the delivery and reduce toxicity may improve outcomes for our patients.'"

Media quote

Dr Johnson on ABBV-011 in Small Cell Lung Cancer (OncLive) - "Melissa L. Johnson, MD...discusses the development of the seizure-related homolog protein 6 (SEZ6)-targeting antibody-drug conjugate (ADC) ABBV-011 and outcomes with this agent in patients with small cell lung cancer (SCLC)....SEZ6 is a new target for patients with SCLC that expands the treatment paradigm beyond DLL3-targeted agents, Johnson concludes."

Video

First-in-human study of ABBV-011, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate, in patients with small cell lung cancer. (ASCO 2023) - P1 | " Phase 1, open-label, multicenter study (NCT03639194) of ABBV-011 alone or in combination with budigalimab, a programmed cell death 1 inhibitor. The MTD was not reached and ABBV-011 was well tolerated at 1.0 mg/kg with promising antitumor activity observed. Further evaluation of ABBV-011 is ongoing. Clinical trial information: NCT03639194."

Clinical • P1 data • Anorexia • Cardiovascular • CNS Disorders • Epilepsy • Fatigue • Hematological Disorders • Hepatology • Hypertension • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Portal Hypertension • Pulmonary Disease • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

ABBV-011 Achieves Antitumor Activity and Tolerable Safety in Small Cell Lung Cancer (Targeted Oncology) - P1 | N=132 | NCT03639194 | Sponsor: AbbVie | "Results from a first-in-human phase 1 trial (NCT03639194) shows that ABBV-011, a SEZ6-targeted antibody-drug conjugate (ADC), given every 3 weeks at 1 mg/kg was well-tolerated and achieved early efficacy in patients with relapsed or refractory small cell lung cancer (SCLC), according to a presentation at the 2023 ASCO Annual Meeting....In all patients (n = 98), ABBV-011 elicited a confirmed objective response rate (ORR) of 19% (95% CI, 12%-29%), with a clinical benefit rate (CBR) of 69% (95% CI, 59%-78%). Thirty-seven percent (95% CI, 27%-47%) of patients experienced a CBR that lasted for longer than 12 weeks....The median progression-free survival (PFS) was 3.5 months (95% CI, 1.5-4.2) in all patients who received the agent at 1 mg/kg."

P1 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study of ABBV-011 Alone and in Combination With Budigalimab (ABBV-181) in Participants With Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=132 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting | N=233 ➔ 132

Combination therapy • Enrollment change • Enrollment closed • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Protective effect of anti-idiopathic pulmonary fibrosis drug Pirfenidone and Sufenidone (SC1011) on pulmonary injury induced by tuberculosis in a mouse tuberculosis model (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "A total of 75 C57BL/6 mice were infected with 1×10 CFU/ml H37Rv suspension by aerosol and randomly divided into untreated (n=9) group, isoniazid+rifampicin+pyrazinamide (HRZ) group (n=22), PFD+HRZ group (n=22), and SC1011+HRZ group (n=22). PFD/SC1011, when combined with HRZ, reduced lung injury and reduced secondary fibrosis in pulmonary tuberculosis in C57BL/6 mice. SC1011 combined with HRZ has no significant short-term therapeutic effect on MTB, but may reduce its recurrence rate in long-term treatment, especially in reducing the recurrence rate of mouse spleen."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IFNG • TNFA

ABBV-011, A Novel, Calicheamicin-Based Antibody-Drug Conjugate, Targets SEZ6 to Eradicate Small Cell Lung Cancer Tumors. (PubMed, Mol Cancer Ther) - P1 | "We developed an antibody targeting SEZ6 that is rapidly internalized upon receptor binding and, when conjugated to the calicheamicin linker drug, drives potent tumor regression in vitro and in vivo. These preclinical data suggest that ABBV-011 may provide a novel treatment for patients with SCLC and a rationale for ongoing phase I studies (NCT03639194)."

Journal • CNS Disorders • Epilepsy • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study of ABBV-011 Alone and in Combination With Budigalimab (ABBV-181) in Participants With Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov) - P1; N=200; Recruiting; Sponsor: AbbVie; Trial completion date: May 2025 ➔ Jul 2024; Trial primary completion date: May 2025 ➔ Jul 2024

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

""The antibody part of SC-011 binds to a protein on some SCLC cells called SEZ6"" (@BertrandBio)

Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

"Any ideas what $ABBV ABBV-011 is? Son of Rova-T perhaps? TIA" (@JacobPlieth)

A Study of ABBV-011 Alone and in Combination With Budigalimab (ABBV-181) in Participants With Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov) - P1; N=188; Recruiting; Sponsor: AbbVie; Trial completion date: May 2023 ➔ Mar 2025; Trial primary completion date: May 2023 ➔ Mar 2025

Trial completion date • Trial primary completion date • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study of ABBV-011 Alone and in Combination With Budigalimab (ABBV-181) in Participants With Relapsed or Refractory Small Cell Lung Cancer (clinicaltrials.gov) - P1; N=188; Recruiting; Sponsor: AbbVie; Trial completion date: Sep 2023 ➔ May 2023; Trial primary completion date: Sep 2023 ➔ May 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Newly added product (AbbVie Press Release) - P1, Small cell lung cancer

Pipeline update