NCT03036228: MASTIFF

MTH1, A Phase I, Study on Tumors Inhibition, First in Human, First in Class

Completed Phase 1 Last updated 9 September 2025

What this trial tests

Phase 1 trial testing Karonudib in Cancer in 63 participants. Completed in 17 December 2024.

Timeline

14 January 2017

Primary endpoint
17 December 2024

17 December 2024

Quick facts

Lead sponsor	Thomas Helleday Foundation
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	63
Start date	14 January 2017
Primary completion	17 December 2024
Estimated completion	17 December 2024
Sites	3 locations across Sweden

Drugs / interventions tested

• Karonudib — full drug profile →

Conditions studied

• Cancer — all drugs for Cancer →

Sponsor

Thomas Helleday Foundation

Who can join

Adults 18 to 75, any sex, with Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Primary Objective

• To determine the safety and tolerability of Karonudib (TH1579) in escalating doses for the treatment of patients with advanced solid malignant tumours.

Secondary Objective

* To define DLT and MTD.
* To determine a recommended phase 2 dose (RP2D) and schedule.
* To determine the pharmacokinetics of Karonudib.
* To determine preliminary signs of clinical efficacy of Karonudib.
* To determine overall survival.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting the DNA damage response and repair in cancer through nucleotide metabolism.
   Helleday T, Rudd SG. · · 2022 · cited 36× · PMID 35583750 · DOI 10.1002/1878-0261.13227
2. A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma.
   Einarsdottir BO, Karlsson J, Söderberg EMV, Lindberg MF, et al · · 2018 · cited 35× · PMID 30042422 · DOI 10.1038/s41419-018-0865-6
3. TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model.
   Moukengue B, Brown HK, Charrier C, Battaglia S, et al · · 2020 · cited 34× · PMID 32151797 · DOI 10.1016/j.ebiom.2020.102704
4. Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.
   Yin Y, Chen F. · · 2020 · cited 29× · PMID 33354500 · DOI 10.1016/j.apsb.2020.02.012
5. Potent and specific MTH1 inhibitors targeting gastric cancer.
   Zhou W, Ma L, Yang J, Qiao H, et al · · 2019 · cited 27× · PMID 31164636 · DOI 10.1038/s41419-019-1665-3
6. MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.
   Sanjiv K, Calderón-Montaño JM, Pham TM, Erkers T, et al · · 2021 · cited 24× · PMID 34593524 · DOI 10.1158/0008-5472.can-21-0061
7. <i>In silico</i> Druggability Assessment of the NUDIX Hydrolase Protein Family as a Workflow for Target Prioritization.
   Michel M, Homan EJ, Wiita E, Pedersen K, et al · · 2020 · cited 19× · PMID 32548091 · DOI 10.3389/fchem.2020.00443
8. Role of MTH1 in oxidative stress and therapeutic targeting of cancer.
   Taiyab A, Ashraf A, Sulaimani MN, Rathi A, et al · · 2024 · cited 18× · PMID 39418911 · DOI 10.1016/j.redox.2024.103394