A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301)

Spiliopoulou, Pavlina; Kazmi, Farasat; Aroldi, Francesca; Holmes, Thomas; Thompson, David; Griffiths, Lucinda; Qi, Cathy; Parkes, Matthew; Lord, Simon; Veal, Gareth J.; Harrison, David J.; Coyle, Vicky M.; Graham, Jill; Jeffry Evans, Thomas R.; Blagden, Sarah P.

doi:10.1186/s13046-024-03010-1

Journal of Experimental & Clinical Cancer Research

Table 4 NUC-3373 plasma PK parameters on Day 1 and Day 15

From: A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301)

Dose / infusion duration/ Regimen	Parameter	C_max (mg/mL)	AUC_last (h*mg/L)	AUC_(0-∞) (h*mg/L)	T_1/2 (h)	AUC_{last_D} (h*mg/L/mg)	AUC_{(0-∞)_D} (h*mg/L/mg)
Day 1
500 mg/m² 30 mins Q1W	N	5	5	5	5	5	5
	Geometric mean	32.54	56.68	70.83	12.21	0.057	0.072
	Geo lower 1SD	22.47	33.08	44.05	4.65	0.033	0.044
	Geo upper 1SD	47.14	97.12	113.89	32.06	0.100	0.117
1125 mg/m² 2 hours Q1W	N	3	3	3	3	3	3
	Geometric mean	38.66	72.31	77.47	12.51	0.038	0.041
	Geo lower 1SD	29.65	47.40	51.31	9.61	0.026	0.028
	Geo upper 1SD	50.39	110.31	116.97	16.27	0.056	0.061
1875 mg/m² 4 hours Q1W	N	6	6	6	6	6	6
	Geometric mean	25.50	105.59	111.25	8.74	0.032	0.033
	Geo lower 1SD	18.36	60.27	60.67	3.43	0.019	0.019
	Geo upper 1SD	35.43	184.97	204.01	22.28	0.052	0.058
1875 mg/m² 4 hours Q2W	N	3	3	3	3	3	3
	Geometric mean	29.05	123.84	125.49	3.39	0.038	0.038
	Geo lower 1SD	26.01	96.77	97.22	1.13	0.033	0.033
	Geo upper 1SD	32.44	158.47	161.98	10.19	0.044	0.045
2500 mg/m² 4 hours Q1W	N	6	6	6	6	6	6
	Geometric mean	38.11	172.47	174.21	3.77	0.038	0.038
	Geo lower 1SD	28.80	116.50	116.72	1.74	0.024	0.024
	Geo upper 1SD	50.44	255.33	260.01	8.17	0.059	0.060
2500 mg/m² 4 hours Q2W	N	5	5	5	5	4	4
	Geometric mean	43.48	201.76	204.93	5.91	0.046	0.047
	Geo lower 1SD	30.64	124.32	124.14	4.46	0.027	0.026
	Geo upper 1SD	61.71	327.44	338.27	7.85	0.081	0.083
3250 mg/m² 4 hours Q1W	N	3	3	3	3	3	3
	Geometric mean	35.50	150.98	151.75	3.71	0.024	0.024
	Geo lower 1SD	22.46	90.69	91.38	3.05	0.014	0.014
	Geo upper 1SD	56.11	251.36	251.99	4.53	0.041	0.041
Day 15
1875 mg/m² 4 hours Q1W	N	6	6	6	6	6	6
	Geometric mean	29.68	126.38	130.22	5.59	0.040	0.041
	Geo lower 1SD	21.13	88.19	86.37	3.64	0.025	0.025
	Geo upper 1SD	41.68	181.11	196.34	8.59	0.063	0.068
1875 mg/m² 4 hours Q2W	N	3	3	3	3	3	3
	Geometric mean	27.05	116.39	117.87	2.82	0.036	0.036
	Geo lower 1SD	22.09	73.36	73.74	0.97	0.024	0.025
	Geo upper 1SD	33.13	184.66	188.41	8.22	0.052	0.053
2500 mg/m² 4 hours Q1W	N	6	6	6	6	6	6
	Geometric mean	39.65	170.48	176.93	4.47	0.037	0.039
	Geo lower 1SD	28.58	112.15	113.84	1.93	0.023	0.024
	Geo upper 1SD	55.02	259.17	275.01	10.32	0.060	0.063
2500 mg/m² 4 hours Q2W	N	3	3	3	3	3	3
	Geometric mean	37.36	177.94	180.17	4.95	0.040	0.040
	Geo lower 1SD	23.39	91.64	91.69	4.54	0.021	0.021
	Geo upper 1SD	59.64	345.51	354.00	5.40	0.076	0.078
3250 mg/m² 4 hours Q2W	N	2	2	1	1	2	1
	Geometric mean	36.92	136.67	164.37	4.59	0.021	0.026
	Geo lower 1SD	32.91	105.64	–	–	0.016	–
	Geo upper 1SD	41.42	176.83	–	–	0.028	–

AUC_(0-∞) area under the plasma concentration-time curve from time 0 to infinity, AUC_{(0-∞)_D} dose normalized AUC_(0-∞), AUC_last area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration, AUC_{last_D} dose normalized AUC_last, C_max maximum plasma concentration, Q1W weekly, Q2W alternate weekly, T_1/2 half-life.
Geo lower and Geo upper 1 Standard deviation (SD) – 68% range of the geometric mean

Back to article page

ISSN: 1756-9966

Contact us

Submission enquiries: Access here and click Contact Us
General enquiries: info@biomedcentral.com