NCT05276284: TEMPLE

Thiopurine Enhanced Mutations for PD-1/Ligand-1 Efficacy

Completed Phase 1, PHASE2 Last updated 14 January 2026

What this trial tests

Phase 1, PHASE2 trial testing Atezolizumab, 6-mercaptopurine, 6-thioguanine in Solid Tumor, Adult in 18 participants. Completed in 1 September 2025.

Timeline

1 September 2022

Primary endpoint
31 December 2024

1 September 2025

Quick facts

Lead sponsor	Kristoffer Rohrberg
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	18
Start date	1 September 2022
Primary completion	31 December 2024
Estimated completion	1 September 2025
Sites	1 location across Denmark

Drugs / interventions tested

• Atezolizumab, 6-mercaptopurine, 6-thioguanine

Conditions studied

• Solid Tumor, Adult — all drugs for Solid Tumor, Adult →
• Metastatic Cancer — all drugs for Metastatic Cancer →

Sponsor

Kristoffer Rohrberg

Who can join

18 and older, any sex, with Solid Tumor, Adult or Metastatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The TEMPLE study is a single-center prospective phase Ib and II trial to determine the safety, tolerability and efficacy of Atezolizumab given in combination with thiopurine therapy (6-mercaptopurine and 6-thioguanine) in patients with advanced and/or metastatic solid tumors with an intermediate tumor mutational burden.

Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) will be determined in a single armed, open label phase Ib trial with a fixed dose of Atezolizumab in combination with thiopurine therapy with a dose-limiting toxicity (DLT) period of 4 weeks. A total of 27-39 patients will be enrolled in the TEMPLE study. Phase Ib will enroll 3-18 patients depending on the number of DLTs and need for dose de-escalation. Data from patients treated in the phase Ib study at RP2D will be included when assessing endpoints in the phase II part of the study. Phase II will enroll a total of 27 patients (including 3-6 patients treated at RP2D in the phase I part of the trial) in a Simon's 2 stage design (13 in stage 1 and 14 in stage 2).

Publications & conference data

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

1. Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases.
   Hwang JT, Lee A, Kho C. · · 2022 · cited 49× · PMID 35563444 · DOI 10.3390/ijms23095053
2. Thiopurine 6TG treatment increases tumor immunogenicity and response to immune checkpoint blockade.
   Nazerai L, Willis SC, Yankilevich P, Di Leo L, et al · · 2023 · cited 7× · PMID 36545256 · DOI 10.1080/2162402x.2022.2158610
3. Safety of Immunomodulatory Systemic Therapies Used in the Management of Immune-Related Cutaneous Adverse Events.
   Gu SL, Nath S, Markova A. · · 2023 · cited 6× · PMID 38004475 · DOI 10.3390/ph16111610
4. An analysis pipeline for understanding 6-thioguanine effects on a mouse tumour genome.
   Yankilevich P, Nazerai L, Willis SC, Schmiegelow K, et al · · 2024 · cited 2× · PMID 38279992 · DOI 10.1007/s00262-023-03610-4
5. Thiopurine therapy enhances immune checkpoint inhibitor efficacy in low-mutational burden melanoma: A promising anticancer approach.
   Nazerai L, Tsiavou C, Vardouli L, Schmiegelow K, et al · · 2025 · cited 1× · PMID 39993201 · DOI 10.1073/pnas.2423246122
6. Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.
   Zhang S, Li J, Chen M, Huang H. · · 2026 · PMID 41978829 · DOI 10.1002/mco2.70729
7. Immune Cell Modulation of Patient-Matched Organoid Drug Response in Precision Cancer Medicine Platform.
   Kjølle S, Presti M, Roque JP, Bisgaard LH, et al · · 2026 · PMID 41677622 · DOI 10.3390/cells15030259