AGS-16C3F / Astellas, Pfizer - LARVOL DELTA

ADCs and Radiotherapeutics Represent Novel Treatment Methods in RCC (OncLive) - "'We still have a lot to learn about ADCs. They're very provocative and certainly have demonstrated a lot of activity across multiple other tumor [types] with a lot of excitement,' McKay noted. 'However, RCC is a tumor type that does not traditionally respond to chemotherapy, so we need to understand what [would be] the right payload.'...Finally, McKay pointed to the investigation of TPST-1120, which is a first-in-class oral PPARa inhibitor. In a phase 1 study (NCT03829436), single-agent treatment produced an ORR of 23% in patients with solid tumors (n = 13). Among the 3 partial responses observed, 2 patients had RCC and progressed on prior anti–PD-1 therapy."

Media quote • Renal Cell Carcinoma

ADCs and Radiotherapeutics Represent Novel Treatment Methods in RCC (OncLive) - P2 | N=133 | NCT02639182 | Sponsor: Astellas Pharma Global Development, Inc. | "AGS-16C3F is another novel ADC designed to target ENPP3, which is expressed in 94% of patients with ccRCC. In a phase 2 trial...that compared the ADC vs axitinib (Inlyta) in previously treated patients with metastatic RCC, the primary end point of PFS was not met. Patients treated with AGS-16C3F experienced a median PFS of 2.9 months vs 5.7 months for axitinib (HR, 1.676; 95% CI, 1.107-2.537; P = .015)."

P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma (clinicaltrials.gov) - P2; N=133; Completed; Sponsor: Astellas Pharma Global Development, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Randomized Phase II Study of AGS-16C3F Versus Axitinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma. (PubMed, Oncologist) - "The investigational compound, AGS-16C3F, did not meet the primary endpoint of this trial. These study results provide a benchmark for axitinib use in heavily pretreated patients with mRCC."

Clinical • Journal • P2 data • Fatigue • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma (clinicaltrials.gov) - P2; N=134; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: Sep 2021 ➔ Sep 2020; Trial primary completion date: Sep 2021 ➔ Aug 2019

Clinical • Trial completion date • Trial primary completion date

In vitro and in vivo efficacy of an anti-CD203c conjugated antibody (AGS-16C3F) in mouse models of advanced systemic mastocytosis. (PubMed, Blood Adv) - "Furthermore, animals treated with AGS-16C3F had prolonged survival compared with the animals treated with control ADC, and AGS-16C3F efficiently prevented disease relapse. In conclusion, these preclinical studies identified CD203c as a novel therapeutic target on neoplastic MCs, and AGS-16C3F as a promising ADC for the treatment of patients with AdvSM."

Journal • Preclinical

Phase 1 Trials of anti-ENPP3 antibody drug conjugates in advanced refractory renal cell carcinomas. (PubMed, Clin Cancer Res) - "AGS-16C3F was tolerated and had durable antitumor activity at 1.8 mg/kg every 3 weeks."

Journal • P1 data

A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma (clinicaltrials.gov) - P2; N=134; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: Jun 2019 ➔ Sep 2021; Trial primary completion date: Jun 2019 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date

Modulation of Macropinocytosis-Mediated Internalization Decreases Ocular Toxicity of Antibody-Drug Conjugates. (PubMed, Cancer Res) - "AGS-16C3F is an antibody-drug conjugate (ADC) against ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) containing the mcMMAF linker-payload currently in development for treatment of metastatic renal cell carcinoma...Both molecules displayed similar anti-tumor activity in a mouse xenograft model. These findings establish a mechanism of action for target-independent toxicities of AGS-16C3F and ADCs in general, and provide methods to ameliorate these toxicities."

Journal

A Study of AGS-16C3F vs. Axitinib in Metastatic Renal Cell Carcinoma (clinicaltrials.gov) - P2; N=134; Active, not recruiting; Sponsor: Astellas Pharma Global Development, Inc.; Trial completion date: Mar 2019 ➔ Jun 2019; Trial primary completion date: Mar 2019 ➔ Jun 2019

Clinical • Trial completion date • Trial primary completion date