ABBV-706 / AbbVie - LARVOL DELTA

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=180 | Not yet recruiting | Sponsor: AbbVie | N=730 ➔ 180 | Trial completion date: Sep 2031 ➔ May 2029 | Trial primary completion date: Sep 2031 ➔ May 2029

Adverse events • Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Efficacy of ABBV-706 as second-line treatment for patients with platinum-refractory/resistant small cell lung cancer (ESMO 2025) - P1 | "Background First-line (1L) standard of care (SOC) for extensive-stage small cell lung cancer (SCLC) includes platinum chemotherapy + etoposide (PE), with a PD-L1 inhibitor...Cross-trial comparison showed that ABBV-706 had improved efficacy (ORR, DOR, and PFS) compared with approved 2L agents lurbinectedin and topotecan...Given the antitumor effect observed in PDX models and improved outcomes in PE-resistant pts from NCT05599984, ABBV-706 has the potential to replace 1L SOC in SCLC. Table: 2777P Efficacy observed in NCT05599984 Clinical trial pts N=80 1.8 mg/kg n=41 2.5 mg/kg n=39 CTFI <30 days n=19 CTFI <90 days n=41 ORR, % (n/N) 56 (23/41) 59 (23/39) 53 (10/19) 59 (24/41) mDOR, months [95% CI] 6.2 [4.2, NE] 4.4 [3.5, 6.9] 5.7 [2.8, NE] 5.6 [3.2, 6.9] Median PFS-706, months [95% CI] 6.8 [4.0, 8.2] 5.6 [4.4, 7.0] 5.7 [3.9, 7.5] 5.7 [4.2, 7.0] Median PFS-L1, months [95% CI] 6.1 [4.6, 8.8] 6.5 [4.8, 8.4] 4.0 [3.0, 6.0] 4.4 [4.2, 5.5] CTFI, chemotherapy-free..."

Clinical • Lung Cancer • Oncology • 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=288 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • First-in-human • Monotherapy • Brain Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oligodendroglioma • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EGFR • 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) - P1 | "Table: 2778P ctDNA methylation-based molecular response Analysis set,* % (n) RECIST responders, % (n) Methyl cTF reduction from baseline Methyl cTF reduction from baseline 50% 100% 50% 100% 1.8 mg/kg 92 (22/24) 50 (12/24) 100 (14/14) 71 (10/14) 2.5 mg/kg 94 (17/18) 61 (11/18) 100 (13/13) 69 (9/13) *Pts with ctDNA at relevant time point C3D1, from 3 January 2025 data cutoff were included in this analysis. cTF, circulating tumor fraction."

Biomarker • Clinical • IO biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CTCs • SEZ6

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...Legal entity responsible for the study AbbVie, Inc. Funding 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

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

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