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.

3001 Background: SEZ6 is a transmembrane protein expressed in small cell lung cancer (SCLC) and other neuroendocrine neoplasms (NENs), and central nervous system (CNS) tumors. These malignancies have a high unmet need for novel effective therapies. ABBV-706 is an ADC targeting SEZ6 conjugated to a topoisomerase 1 inhibitor payload at a drug-to-antibody ratio of 6, and is highly efficacious in preclinical models of SCLC, NENs, and CNS tumors. Here, results from ABBV-706 monotherapy dose escalation (DE) are presented. Methods: 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. Primary objectives are to determine the safety, PK, preliminary efficacy, and recommended phase 2 dose of ABBV-706. Exploratory objectives are to assess SEZ6 expression retrospectively and its association with safety, PK, and efficacy. DE enrolled adults (≥18 yr) with relapsed/refractory SCLC, high-grade CNS tumors, and high-grade NENs, following the Bayesian optimal interval design. ABBV-706 was administered IV at 1.3–3.5 mg/kg doses Q3W in 21-d cycles. Results: As of data cutoff on Nov 15, 2023, 49 pts (SCLC: n=22 [45%]; CNS tumors: n=5 [10%]; NEN: n=22 [45%]) were enrolled and treated with ABBV-706 in DE and backfill cohorts. Median age was 64 yr (range 32–81) and median prior lines of therapy was 2.5 (range 1–6). 2 pts had a dose-limiting toxicity: 1 G4 leukopenia and neutropenia lasting >7 d at 3.0 mg/kg and 1 G4 thrombocytopenia at 3.5 mg/kg. TEAEs occurred in 45 (92%) pts, the most frequent being anemia (51%), fatigue (41%), neutropenia (31%), and leukopenia (31%). G≥3 TEAEs occurred in 28 (57%) pts and were mainly hematologic: neutropenia (29%), anemia (27%), and leukopenia (25%). No pneumonitis/interstitial lung disease was observed. Gastrointestinal TEAEs (all G1/2) were seen in 55% of pts, with the most common being nausea (27%) and vomiting (18%). There were no ABBV-706–related deaths. The maximum tolerated dose was 3 mg/kg IV Q3W. ABBV-706 ADC showed an approximate dose-proportional increase in exposure with an elimination half-life of approximately 7 d across doses. For 33 RECIST-evaluable pts, the confirmed (c) objective response rate was overall 21% (7 partial responses [PRs]); 40% (6/15) for SCLC and 6% (1/18) for NEN. The overall response (c and unconfirmed [u]) rate without confirmation was 45% (7 cPRs/8 uPRs); 73% (6 cPRs/5 uPRs) for SCLC, and 22% (1 cPR/3 uPRs) for NEN. 8 uPRs are pending confirmation and will be reported in the final presentation. The clinical benefit rate was 91% (7 PR, 23 stable disease). No activity was observed in 3/3 pts with high-grade gliomas. Conclusions: ABBV-706 demonstrated a manageable safety profile with promising efficacy in SCLC and NENs. Further evaluation of ABBV-706 is ongoing. Clinical trial information: NCT05599984 .

Background:

The 2024 ASCO Annual Meeting Abstracts (a supplement to Journal of Clinical Oncology) is an enduring record of the more than 3,000 abstracts selected by the ASCO Scientific Program Committee for presentation as part of the ASCO Annual Meeting. The meeting was titled “The Art and Science of Cancer Care: From Comfort to Cure” and was held from May 31 to June 4, 2024. The publication includes a Guide to Abstracts listing multiple session categories (e.g., Breast Cancer, Care Delivery, Central Nervous System Tumors, etc.), a Letter From the Editor, and the ASCO Abstracts Policy.

Methods:

No specific research methodology is described in the provided text. The text consists entirely of front matter, editorial information, copyright notices, and policies for the abstract compilation. For reviews: N/A – Review article.

Results:

The text lists the abstract session categories covered in the supplement, including Plenary Session, Special Clinical Science Symposia, and disease‑specific tracks such as Breast Cancer—Local/Regional/Adjuvant, Breast Cancer—Metastatic, Care Delivery/Models of Care, Central Nervous System Tumors, Developmental Therapeutics, Gastrointestinal Cancer, Genitourinary Cancer, Gynecologic Cancer, Head and Neck Cancer, Hematologic Malignancies, Lung Cancer, Medical Education, Melanoma/Skin Cancers, Pediatric Oncology, Prevention/Risk Reduction/Genetics, Quality Care/Health Services Research, Sarcoma, and Symptom Science/Palliative Care. The Editor’s Letter notes that publication‑only abstracts are included in the online supplement to the June 1 issue of Journal of Clinical Oncology at ASCOPubs.org.

Data Summary:

More than 3,000 abstracts were selected by the ASCO Scientific Program Committee. The public release schedule: most abstracts were released at 5:00 PM EDT on Thursday, May 23, 2024; Late‑Breaking Abstracts presented in a scientific presentation on Friday, May 31, were released Friday, May 31, at 8:00 AM EDT.

Conclusions:

The provided text does not contain a specific study’s conclusions. It is an introductory compilation for the meeting abstracts.

Practical Significance:

The abstracts serve as a resource for clinicians and researchers, providing information on the latest cancer care research. The online access through ASCO Meeting Experience (meetings.asco.org) and the citation format (J Clin Oncol 42, 2024 (suppl 16; abstr X)) allow for easy retrieval and reference in clinical practice and further research.