INDUCE-2: A Phase I/II, open-label, two-part study of feladilimab in combination with tremelimumab in patients with advanced solid tumors.

Combining immunotherapies with distinct mechanisms of action has the potential to overcome treatment resistance and improve outcomes. The inducible T-cell co-stimulator (ICOS) agonist feladilimab is directed at enhancing T-cell activation and function, thereby promoting an antitumor response. INDUCE-2 (NCT03693612) was a Phase I/II, open-label, two-part study evaluating the anti-ICOS agonist feladilimab in combination with the anti-CTLA-4 antibody tremelimumab in patients with select advanced solid tumors. Objectives of Part 1 were to determine the safety, tolerability, and recommended phase 2 dose (RP2D) of feladilimab in combination with tremelimumab. In Part 2, the antitumor activity of the combination (administered at the RP2D determined in Part 1) was to be assessed in patients with relapsed/refractory head and neck squamous cell carcinoma. Primary endpoints included the rates of dose-limiting toxicities (DLTs), adverse events (AEs), AEs of special interest, and serious AEs. Secondary endpoints included overall response rate, while biomarker assessment was exploratory. A total of 26 patients were enrolled, 18 (69%) of whom had completed the study at end date. One patient, in the highest dose group (24/225 mg feladilimab/tremelimumab), experienced a DLT 18 days after the first dose of study treatment. All patients experienced at least one AE; AEs led to treatment discontinuation in four (15%) patients. Partial response was observed in one patient. Feladilimab in combination with tremelimumab was well-tolerated but showed limited efficacy. Based on the totality of data from Part 1, it was decided not to continue with Part 2.

Solubility and adsorption behaviors of chlorpyriphos-methyl in the presence of surfactants.

In the present work changes in the adsorption of the pesticide chlorpyrifos-methyl (CLP-m) on soil colloids induced by application of surfactants were determined using a batch equilibrium method. The surfactants used were sodium dodecyl sulphate (SDS), Tween 20, and dihexadecyldimethylammonium bromide (DHAB). The adsorption isotherms of CLP-m in aqueous medium and in surfactant solutions at concentration equal to the critical micelle concentration (CMC) fitted the Freunlich adsorption equation generally with R(2) values greater than 0.96. While the addition of SDS and DHAB decreased the pesticide adsorption, the addition of Tween 20 increased the pesticide adsorption. The increases or decreases in the adsorption in the experiment revealed that the behavior of CLP-m in soil water-systems mainly depends on the type of surfactant. Moreover water solubility of CLP-m changes by the three surfactants below and above their CMC were studied. While the solubility of CLP-m was enhanced by SDS both below and above the CMC, the solubility of the pesticide was enhanced by DHAB only above the CMC. Tween 20 did not influence the solubility of CLP-m.