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Supplementary Figure S17 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies

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posted on 2024-02-01, 08:22 authored by Benedito A. Carneiro, Ludimila Cavalcante, Devalingam Mahalingam, Anwaar Saeed, Howard Safran, Wen Wee Ma, Andrew L. Coveler, Steven Powell, Bruno Bastos, Elizabeth Davis, Vaibhav Sahai, William Mikrut, James Longstreth, Sheri Smith, Taylor Weisskittel, Hu Li, Brittany A. Borden, R. Donald Harvey, Solmaz Sahebjam, Andrés Cervantes, Austin Koukol, Andrew P. Mazar, Neeltje Steeghs, Razelle Kurzrock, Francis J. Giles, Pamela Munster

Best Overall Response by Cancer Histology in Part 1

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Actuate Therapeutics (Actuate Therapeutics Inc)

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ARTICLE ABSTRACT

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. 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. Patients received monotherapy (n = 67) or combination therapy (n = 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 = 62) and part 2 combination (n = 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. 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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