TY - JOUR
T1 - Safety and clinical activity of MEDI0562, a humanized OX40 agonist monoclonal antibody, in adult patients with advanced solid tumors
AU - Glisson, Bonnie S.
AU - Leidner, Rom S.
AU - Ferris, Robert L.
AU - Powderly, John
AU - Rizvi, Naiyer A.
AU - Keam, Bhumsuk
AU - Schneider, Reva
AU - Goel, Sanjay
AU - Ohr, James P.
AU - Burton, Jennifer
AU - Zheng, Yanan
AU - Eck, Steven
AU - Gribbin, Matthew
AU - Streicher, Katie
AU - Townsley, Danielle M.
AU - Patel, Sandip Pravin
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/10/15
Y1 - 2020/10/15
N2 - Purpose: Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-inhuman study evaluated MEDI0562 in adults with advanced solid tumors. Patients and Methods: In this phase I, multicenter, open-label, single-arm, dose-escalation (3þ3 design) study, patients received 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg MEDI0562 through intravenous infusion every 2 weeks, until confirmed disease progression or unacceptable toxicity. The primary objective evaluated safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics. Results: In total, 55 patients received ≥1 dose of MEDI0562 and were included in the analysis. The most common tumor type was squamous cell carcinoma of the head and neck (47%). Median duration of treatment was 10 weeks (range, 2-48 weeks). Treatment-related adverse events (TRAEs) occurred in 67% of patients, most commonly fatigue (31%) and infusion-related reactions (14%). Grade 3 TRAEs occurred in 14% of patients with no apparent dose relationship; no TRAEs resulted in death. Two patients had immune-related partial responses per protocol and 44% had stable disease. MEDI0562 induced increased Ki67þ CD4þ and CD8þ memory T-cell proliferation in the periphery and decreased intratumoral OX40þ FOXP3þ cells. Conclusions: MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pretreated patients. On-target pharmacodynamic effects were suggested in this setting. Further evaluation with immune checkpoint inhibitors is ongoing.
AB - Purpose: Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized mAb, specifically binds to the costimulatory molecule OX40. This first-inhuman study evaluated MEDI0562 in adults with advanced solid tumors. Patients and Methods: In this phase I, multicenter, open-label, single-arm, dose-escalation (3þ3 design) study, patients received 0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg MEDI0562 through intravenous infusion every 2 weeks, until confirmed disease progression or unacceptable toxicity. The primary objective evaluated safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics. Results: In total, 55 patients received ≥1 dose of MEDI0562 and were included in the analysis. The most common tumor type was squamous cell carcinoma of the head and neck (47%). Median duration of treatment was 10 weeks (range, 2-48 weeks). Treatment-related adverse events (TRAEs) occurred in 67% of patients, most commonly fatigue (31%) and infusion-related reactions (14%). Grade 3 TRAEs occurred in 14% of patients with no apparent dose relationship; no TRAEs resulted in death. Two patients had immune-related partial responses per protocol and 44% had stable disease. MEDI0562 induced increased Ki67þ CD4þ and CD8þ memory T-cell proliferation in the periphery and decreased intratumoral OX40þ FOXP3þ cells. Conclusions: MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pretreated patients. On-target pharmacodynamic effects were suggested in this setting. Further evaluation with immune checkpoint inhibitors is ongoing.
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U2 - 10.1158/1078-0432.CCR-19-3070
DO - 10.1158/1078-0432.CCR-19-3070
M3 - Article
C2 - 32816951
AN - SCOPUS:85096057790
SN - 1078-0432
VL - 26
SP - 5358
EP - 5367
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -