TY - JOUR
T1 - Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3b Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
AU - Carneiro, Benedito A.
AU - Cavalcante, Ludimila
AU - Mahalingam, Devalingam
AU - Saeed, Anwaar
AU - Safran, Howard
AU - Ma, Wen Wee
AU - Coveler, Andrew L.
AU - Powell, Steven
AU - Bastos, Bruno
AU - Davis, Elizabeth
AU - Sahai, Vaibhav
AU - Mikrut, William
AU - Longstreth, James
AU - Smith, Sheri
AU - Weisskittel, Taylor
AU - Li, Hu
AU - Borden, Brittany A.
AU - Harvey, R. Donald
AU - Sahebjam, Solmaz
AU - Cervantes, Andres
AU - Koukol, Austin
AU - Mazar, Andrew P.
AU - Steeghs, Neeltje
AU - Kurzrock, Razelle
AU - Giles, Francis J.
AU - Munster, Pamela
N1 - Publisher Copyright:
©2023 American Association for Cancer Research.
PY - 2024/2/1
Y1 - 2024/2/1
N2 - Purpose: The safety, pharmacokinetics, and efficacy of elraglusib, a glycogen synthase kinase-3β (GSK-3β) small-molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied. Patients and Methods: Elraglusib (intravenously twice weekly in 3-week cycles) monotherapy dose escalation was followed by dose escalation with eight chemotherapy regimens (gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin, and pemetrexed/carboplatin) in patients previously exposed to the same chemotherapy. Results: Patients received monotherapy (n ¼ 67) or combination therapy (n ¼ 171) elraglusib doses 1 to 15 mg/kg twice weekly. The initial recommended phase II dose (RP2D) of elraglusib was 15 mg/kg twice weekly and was defined, without dose-limiting toxicity observation, due to fluid volumes necessary for drug administration. The RP2D was subsequently reduced to 9.3 mg/kg once weekly to reduce elraglusib-associated central/ peripheral vascular access catheter blockages. Other common elraglusib-related adverse events (AE) included transient visual changes and fatigue. Grade ≥3 treatment-emergent AEs occurred in 55.2% and 71.3% of patients on monotherapy and combination therapy, respectively. Part 1 monotherapy (n ¼ 62) and part 2 combination (n ¼ 138) patients were evaluable for response. In part 1, a patient with melanoma had a complete response, and a patient with acute T-cell leukemia/lymphoma had a partial response (PR). In part 2, seven PRs were observed, and the median progression-free survival and overall survival were 2.1 [95% confidence interval (CI), 2–2.6] and 6.9 (95% CI, 5.7–8.4) months, respectively. Conclusions: Elraglusib had a favorable toxicity profile as monotherapy and combined with chemotherapy and was associated with clinical benefit supporting further clinical evaluation in combination with chemotherapy.
AB - Purpose: The safety, pharmacokinetics, and efficacy of elraglusib, a glycogen synthase kinase-3β (GSK-3β) small-molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied. Patients and Methods: Elraglusib (intravenously twice weekly in 3-week cycles) monotherapy dose escalation was followed by dose escalation with eight chemotherapy regimens (gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin, and pemetrexed/carboplatin) in patients previously exposed to the same chemotherapy. Results: Patients received monotherapy (n ¼ 67) or combination therapy (n ¼ 171) elraglusib doses 1 to 15 mg/kg twice weekly. The initial recommended phase II dose (RP2D) of elraglusib was 15 mg/kg twice weekly and was defined, without dose-limiting toxicity observation, due to fluid volumes necessary for drug administration. The RP2D was subsequently reduced to 9.3 mg/kg once weekly to reduce elraglusib-associated central/ peripheral vascular access catheter blockages. Other common elraglusib-related adverse events (AE) included transient visual changes and fatigue. Grade ≥3 treatment-emergent AEs occurred in 55.2% and 71.3% of patients on monotherapy and combination therapy, respectively. Part 1 monotherapy (n ¼ 62) and part 2 combination (n ¼ 138) patients were evaluable for response. In part 1, a patient with melanoma had a complete response, and a patient with acute T-cell leukemia/lymphoma had a partial response (PR). In part 2, seven PRs were observed, and the median progression-free survival and overall survival were 2.1 [95% confidence interval (CI), 2–2.6] and 6.9 (95% CI, 5.7–8.4) months, respectively. Conclusions: Elraglusib had a favorable toxicity profile as monotherapy and combined with chemotherapy and was associated with clinical benefit supporting further clinical evaluation in combination with chemotherapy.
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U2 - 10.1158/1078-0432.CCR-23-1916
DO - 10.1158/1078-0432.CCR-23-1916
M3 - Article
C2 - 37982822
AN - SCOPUS:85184146802
SN - 1078-0432
VL - 30
SP - 522
EP - 531
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -