ABBV-303 / AbbVie, Dragonfly Therap - LARVOL DELTA

AbbVie halts development of Dragonfly cancer asset midflight (FierceBiotech) - "'We have terminated clinical activity around ABBV-303,'...alluding to a phase 1 solid tumor trial of the natural killer (NK) cell engager. 'However, our partnership with Dragonfly is still ongoing'. The study was terminated in light of 'strategic considerations,' according to its entry on the federal trial database clinicaltrials.gov."

Discontinued • Trial termination • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

ABBV-303 is a Natural Killer Cell Engager Specific for c-Met-Expressing Tumors. (PubMed, Cancer Res) - "When compared to a CD3 bispecific with the same c-Met binder, ABBV-303 drove lower levels of inflammatory cytokines at equivalent levels of tumor cell killing and enhanced tolerance of normal cells expressing c-Met, consistent with the natural tendency of NK cells to preferentially react with stressed or cancer cells as compared to normal, healthy tissue. Together, this study showed that ABBV-303 is effective at driving anti-tumor immunity against a wide range of c-Met expressing tumors."

Journal • Oncology • Solid Tumor • CD34 • CD8 • IL15 • MET • NKG2D

ABBV-303 is a Natural Killer Cell Engager Specific for c-Met-Expressing Tumors (Cancer Res) - "ABBV-303 drove sub-nanomolar redirected killing potency against tumor cells from different solid tumor indications expressing a range of c-Met levels. ABBV-303 demonstrated anti-tumor activity against established xenografts in CD34-humanized, IL-15 transgenic NSG mice and in a c-Met+ tumor explant."

Preclinical • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics, and Efficacy of Intravenous (IV) ABBV-303, as Monotherapy and in Combination With IV Infused Budigalimab (ABBV-181), in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=27 | Terminated | Sponsor: AbbVie | N=192 ➔ 27 | Trial completion date: Jan 2028 ➔ Oct 2025 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2028 ➔ Oct 2025; Strategic considerations

Enrollment change • First-in-human • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

ABBV-303 engages and redirects NK and CD8 T cells to lyse c-Met expressing tumor cells (SITC 2024) - P1 | "Conclusions Overall, our preclinical studies of ABBV-303 demonstrate drug-mediated tumor cell killing and corresponding immune activation supporting clinical testing of this agent. ABBV-303 is currently being tested in a Phase 1 First-in-Human clinical trial in solid tumors as a monotherapy and in combination with an anti-PD-1 checkpoint inhibitor (NCT06158958)."

IO biomarker • Tumor cell • Oncology • Solid Tumor • CD69 • CD8 • FCGR3A • IFNG • MET • NKG2D

ABBV-303: A novel NK and CD8 T cell engager specific for c-Met-expressing tumors (AACR 2024) - "ABBV-303 includes three functional arms: (1) a c-Met binding scFv based on ABT-700, common to c-Met-targeting antibody-drug conjugates ABBV-400 and Teliso-V; (2) a Fab arm that binds NKG2D, a stimulatory receptor expressed by NK cells and activated CD8+ T cells; and (3) a heterodimeric IgG1 Fc which binds CD16a on NK cells and links the other two binding moieties. A benign safety profile was observed in non-human primates through three repeat doses up to 150 mg/kg given every two weeks, with antibody-like exposures and a serum half-life around 8 days. Based on these findings, the First in Human ABBV-303 study will initiate in 1H 2024 in solid tumors as a monotherapy and in combination with an anti-PD-1 checkpoint inhibitor.All authors are current employees of AbbVie."

Oncology • Solid Tumor • CD34 • CD8 • FCGR3A • MET • NKG2D

Dragonfly has Received Milestone Payment Following Dosing of First Patient in AbbVie Phase 1 Clinical Trial Evaluating DF4101/ABBV-303 (PRNewswire) - "Dragonfly Therapeutics, Inc...announced receipt of a milestone payment following dosing of the first patient in a clinical trial conducted by AbbVie...to evaluate ABBV-303, a solid tumor targeting TriNKET....The Phase 1 clinical trial, conducted by AbbVie, is evaluating ABBV-303 alone and in combination with AbbVie's budigalimab (ABBV-181), in solid tumors."

Financing • Trial status • Oncology • Solid Tumor

A Study of Adverse Events, How Intravenously (IV) Infused ABBV-303 Moves Through the Body, and Change in Disease State, as Monotherapy and in Combination With IV Infused Budigalimab (ABBV-181), in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=181 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study of Adverse Events, How Intravenously (IV) Infused ABBV-303 Moves Through the Body, and Change in Disease State, as Monotherapy and in Combination With IV Infused Budigalimab (ABBV-181), in Adult Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=181 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Combination therapy • Metastases • Monotherapy • New P1 trial • Pan tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck