Fig. 3: ABBV-467 induces tumor regression in xenograft models of MM and AML when combined with venetoclax. | Communications Medicine

Fig. 3: ABBV-467 induces tumor regression in xenograft models of MM and AML when combined with venetoclax.

From: Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients

Fig. 3

Studies were conducted in SCID/bg mice when tumor volume reached ~200 mm3. Each data point represents the group average, with error bars indicating the standard error of the mean. Animals were treated with a ABBV-467 on a QD × 1 dosing schedule in AMO-1 xenografts (n = 8, 50 total animals), or b Q7D × 2 (n = 7, 40 total animals). c OPM-2 xenografts with ABBV-467 on a Q7D × 3 schedule (n = 8, 30 total animals). d Single dose in NCI-H929 xenografts (n = 5, 20 total animals). e OCI-AML2 xenografts treated with venetoclax (QD × 14), 5-azacitidine (Q7D × 3), or in combination (n = 8, 100 total animals). f In vivo efficacy of ABBV-467 in combination with either venetoclax, 5-azacitidine, or the triple combination. g Comparison of survival in mice treated with ABBV-467 + venetoclax or ABBV-467 + venetoclax + 5-azacitidine. h In vivo rescue experiment of venetoclax + 5-azacitidine-treated animals. Two groups of animals were treated with venetoclax + 5-azacitidine until the groups reached an average tumor volume of 1000 mm3 on day 25. One group continued receiving venetoclax + 5-azacitidine, while the other group switched to venetoclax + ABBV-467. i Systemic model of MV4-11 (FLT3-ITD, MLL/AF-4) transduced with red-shifted Luciola italica luciferase under control of the stable UbC promoter (n = 9, 60 total animals). The tumor load is given by the amount of light signal detected, expressed as a photon flux from the whole mouse per second. Tumor load is expressed as a function of time in the absence (vehicle) or presence of treatment with A-694 (Q7D × 3, IV), venetoclax (QD × 21, PO) or in combination. Following treatment with the combination, the tumor load dropped below the detectable limits of the instrument, flux of 2e6, noted by the black horizontal line. j Representative bioluminescent images of the animals from study (i) over time. Animals were size matched on day 6. For days 24 and 31, the mouse in the upper left corner of each image is a negative control (naive mouse injected with D-luciferin). Arrows indicate treatment days. 5-Aza, 5-azacitidine; D, day; FLT3-ITD, FMS-like tyrosine kinase-3 internal tandem duplication; IV, intravenous; MCL-1i, MCL-1 inhibitor; PO, oral; Q, every.

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