ABBV-706 / AbbVie - LARVOL DELTA

AbbVie will also present new analysis from a Phase 1 study of ABBV-706, a SEZ6-directed ADC with a Top1i payload, in relapsed/refractory small cell lung cancer (R/R SCLC) (NCT05599984). (AbbVie Press Release) - "A post hoc analysis on data from R/R SCLC patients enrolled in the study, whose tumors had progressed after two lines of therapy (n=80), was done to compare the anti-cancer effect of ABBV-706 monotherapy vs. platinum-based SOC. All patients in this group had received the platinum-based SOC treatment as first-line therapy (1L SOC)...The findings suggest that ABBV-706 may have the potential to replace the platinum-based SOC as a first-line treatment in SCLC....ABBV-706 treatment also resulted in rapid clearance of circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). Patients with 100% ctDNA clearance had significantly higher PFS and overall survival (OS) vs. patients without ctDNA clearance."

P1 data • Small Cell Lung Cancer

Seizure related 6 homolog (SEZ6) expression pattern and prognostic impact in a real-world cohort of patients with small cell lung cancer (ESMO 2025) - "ABBV-706, is a first-in-class antibody-drug conjugate composed of a potent topoisomerase 1 inhibitor attached via a stable linker to a SEZ6-directed monoclonal antibody, delivering the cytotoxic payload specifically to SEZ6-expressing tumour cells, under investigation for patients with advanced solid tumors, including SCLC...Medical writing support was provided by Payal Jain, PhD, of Avalere Health Global Ltd, funded by AbbVie. Legal entity responsible for the study AbbVie, Inc."

Clinical • IO biomarker • Real-world • Real-world evidence • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • CD276 • DLL3 • NEUROD1 • POU2F3 • SEZ6

ABBV-706, a seizure-related homolog protein 6 (SEZ6)-targeting antibody-drug conjugate (ADC), in patients (pts) with relapsed/refractory (R/R) small cell lung cancer (SCLC): Circulating biomarker and molecular response analyses (ESMO 2025) - No abstract available

Biomarker • Clinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SEZ6

Efficacy of ABBV-706 as second-line treatment for patients with platinum-refractory/resistant small cell lung cancer (ESMO 2025) - No abstract available

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

SEZanne: A Study to Evaluate the Optimal Dose, Adverse Events and Change in Disease Activity of Intravenous ABBV-706 in Combination With Atezolizumab Versus Standard of Care as First-Line Treatment in Adult Participants With Previously Untreated Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P2/3 | N=730 | Not yet recruiting | Sponsor: AbbVie

Adverse events • New P2/3 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Safety and Efficacy of ABBV-706, a Seizure-related Homolog Protein 6-targeting Antibody-drug Conjugate, in R/R SCLC (IASLC-WCLC 2025) - P1 | "ABBV-706 has manageable safety and promising efficacy in patients with R/R SCLC. Based on the totality of the benefit-risk profile, monotherapy RP2D was determined to be 1.8 mg/kg Q3W in SCLC."

Clinical • Anemia • CNS Disorders • Epilepsy • Fatigue • Interstitial Lung Disease • Lung Cancer • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • SEZ6

M23-385: Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=350 | Recruiting | Sponsor: AbbVie | Trial completion date: Nov 2027 ➔ Jun 2026 | Trial primary completion date: Nov 2027 ➔ Jun 2026

Adverse events • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EGFR • SEZ6

Seizure-related homolog 6 (SEZ6) expression and ctDNA methylation profiles in patients with high-grade neuroendocrine carcinomas (NECs)/neuroendocrine tumors (NETs) from a phase 1 study of ABBV-706 in advanced solid tumors. (ASCO 2025) - P1 | "Robust SEZ6 expression was observed with some heterogeneity across histologies of the NEC/NET monotherapy cohort. High ctDNA detection rate at baseline indicates the feasibility of monitoring molecular response longitudinally without an invasive procedure and identifying predictive biomarker(s) for ABBV-706."

Circulating tumor DNA • Clinical • Metastases • P1 data • CNS Disorders • Endocrine Cancer • Epilepsy • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • SEZ6

Safety and efficacy of ABBV-706, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate, in high-grade neuroendocrine neoplasms. (ASCO 2025) - P1 | "ABBV-706 showed preliminary efficacy in several high-grade NENs with a high unmet need, supporting its further development in specific subtypes."

Clinical • Anemia • CNS Disorders • Endocrine Cancer • Epilepsy • Fatigue • Genito-urinary Cancer • Interstitial Lung Disease • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Pneumonia • Prostate Cancer • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • SEZ6

American Oncology Network Announces Research Studies Presented at ASCO 2025 Annual Meeting (GlobeNewswire) - "American Oncology Network (AON)...is pleased to announce that multiple research studies co-authored by AON physicians and leaders were selected for presentation at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, held May 30-June 3 in Chicago."

Clinical data • Breast Cancer • Neuroendocrine Neoplasm

Additional oral presentations will highlight new safety and efficacy data for ABBV-706, a SEZ6-directed ADC with a Top1i payload… (PRNewswire) - P1 | N=350 | NCT05599984 | Sponsor: AbbVie | "In a Phase 1 open-label study of ABBV-706 monotherapy, 64 patients with high-grade neuroendocrine neoplasms (NENs), a diverse group of rare and aggressive solid tumors, received ABBV-706 monotherapy IV at 1.3–3.5 mg/kg once every 3 weeks. The entire cohort had an ORR of 31.3%, and a median DoR of 5.6 months. The most common grade ≥3 TEAEs (cumulative across all dose levels), were anemia (45%), neutropenia (33%), and thrombocytopenia (21%). Additional data will be presented at ASCO."

P1 data • Neuroendocrine Neoplasm • Neuroendocrine Tumor • Solid Tumor

ABBV-969: A first-in-class dual-targeting PSMA-STEAP1 drug conjugate for the treatment of metastatic castrate-resistant prostate cancer (AACR 2025) - P1 | "ABBV-969 is a conjugate of the DVD-Ig with a proprietary topoisomerase-1 (Top1) inhibitor linker-drug identical to that used in two assets in clinical development, ABBV-400, targeting c-Met, and ABBV-706, targeting SEZ6. Furthermore, ABBV-969 is well tolerated in cynomolgus monkeys with bone marrow and gastrointestinal toxicities common to other Top1 inhibitor ADCs. ABBV-969 is currently in dose escalation in a Phase 1 clinical study (NCT06318273)."

Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1 • MET • SEZ6 • STEAP1 • TOP1

M23-385: Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=350 | Recruiting | Sponsor: AbbVie | Trial completion date: May 2027 ➔ Nov 2027 | Trial primary completion date: Oct 2025 ➔ Nov 2027

Adverse events • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EGFR • SEZ6

First-in-human study of ABBV-706, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced solid tumors (AIOM 2024) - P1 | " Ph1, open-label, DE and dose-expansion study(NCT05599984) of ABBV-706(IV, 1.3–3.5mg/kg doses, Q3W, 21d cycles) as monotherapy or in combination with budigalimab(anti-PD1 inhibitor), carboplatin or cisplatin. ABBV-706 demonstrated manageable safety profile with promising efficacy in SCLC and NENs. Further evaluation of ABBV-706 is ongoing."

Clinical • IO biomarker • Metastases • P1 data • Anemia • Brain Cancer • CNS Disorders • CNS Tumor • Endocrine Cancer • Epilepsy • Fatigue • Glioma • Hematological Disorders • Interstitial Lung Disease • Leukopenia • Lung Cancer • Malignant Glioma • Neuroendocrine Tumor • Neutropenia • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • SEZ6

Prevalence and Prognostic Impact of SEZ6 Expression in a Real-World Cohort of Patients with Small-Cell Lung Cancer (IASLC-WCLC 2024) - P1 | "Standard-of-care (SOC) treatment consisted of first-line platinum-based chemotherapy with or without immune checkpoint inhibitors and second-line topotecan/irinotecan or lurbinectedin. Although the sample size was small and the study was limited to a single site, these data support SEZ6 as a potential ADC-targetable biomarker in SCLC. This real-world SCLC cohort could also be used as a borrowed control for the phase 1 single-arm study being conducted in patients with SCLC treated with ABBV-706 to help identify novel predictive biomarkers and interpret the outcomes from the study."

Clinical • IO biomarker • Real-world • Real-world evidence • CNS Disorders • Epilepsy • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • NEUROD1 • SEZ6

First-in-human study of ABBV-706, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced solid tumors. (ASCO 2024) - P1 | " Phase 1, open-label, multicenter, DE and dose-expansion study (NCT05599984) of ABBV-706 as monotherapy or in combination with budigalimab (a programmed cell death 1 inhibitor), carboplatin, or cisplatin. ABBV-706 demonstrated a manageable safety profile with promising efficacy in SCLC and NENs. Further evaluation of ABBV-706 is ongoing."

Clinical • Metastases • P1 data • Anemia • Brain Cancer • CNS Disorders • CNS Tumor • Endocrine Cancer • Epilepsy • Fatigue • Gastrointestinal Disorder • Glioma • Hematological Disorders • Interstitial Lung Disease • Leukopenia • Lung Cancer • Neuroendocrine Tumor • Neutropenia • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia • SEZ6

AbbVie Showcases Robust Solid Tumor Pipeline at ASCO 2024 with New Data from Its Innovative Antibody-Drug Conjugate (ADC) Platform (PRNewswire) - P1 | N=350 | NCT05599984 | Sponsor: AbbVie | "...Early data from the monotherapy dose escalation part of a first-in-human study of ABBV-706, a potential best-in-class SEZ6 directed ADC, will be presented at an oral presentation. The data demonstrate that among a total of 48 efficacy-evaluable patients (23 SCLC and 25 NEN), the overall confirmed objective response rate was 43.8%. Within the SCLC group, the confirmed objective response rate was 60.9%. Among all the 53 enrolled patients at the time of data cut-off, the most common ≥3 TEAEs were neutropenia (42%), anemia (42%), and leukopenia (28%). The ongoing study (NCT05599984) is evaluating ABBV-706 as monotherapy or in combination...in patients with advanced solid tumors, including SCLC and other NENs. Additional data will be presented at the meeting."

P1 data • Neuroendocrine Tumor • Small Cell Lung Cancer

Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=350 | Recruiting | Sponsor: AbbVie | Trial completion date: Oct 2025 ➔ May 2027

Adverse events • Combination therapy • Metastases • Monotherapy • Trial completion date • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EGFR • 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

Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=350 | Recruiting | Sponsor: AbbVie | Trial completion date: Dec 2026 ➔ Oct 2025 | Trial primary completion date: Dec 2026 ➔ Oct 2025

Adverse events • Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EGFR • SEZ6

Phase 1 Study of ABBV-706, Anti-Sez6 Antibody-Drug Conjugate, in Adults With Advanced Solid Tumors (JSMO 2024) - No abstract available

Clinical • Metastases • P1 data • Oncology • Solid Tumor • SEZ6

Phase I study of ABBV-706, an anti-SEZ6 antibody-drug conjugate, alone or in combination in adults with advanced solid tumors (ESMO 2023) - P1 | "The study will evaluate the preliminary safety, tolerability, pharmacokinetics (PK), and antitumor activity of ABBV-706 as monotherapy and in combination with budigalimab (a PD-1 inhibitor), carboplatin, or cisplatin, and determine the recommended phase 2 dose (RP2D) of ABBV-706. Tumor tissue submission for retrospective SEZ6 expression analysis is required. The study began in December 2022 and enrollment is ongoing."

Clinical • IO biomarker • Metastases • P1 data • Brain Cancer • CNS Tumor • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • SEZ6

Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=350 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Combination therapy • Enrollment open • Monotherapy • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EGFR

Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=350 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Combination therapy • Monotherapy • New P1 trial • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EGFR