PMID- 38546220
OWN - NLM
STAT- Publisher
LR  - 20240328
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
DP  - 2024 Mar 28
TI  - Safety, efficacy, and biological data of T cell-enabling oncolytic adenovirus 
      TILT-123 in advanced solid cancers from the TUNIMO monotherapy phase I trial.
LID - 10.1158/1078-0432.CCR-23-3874 [doi]
AB  - PURPOSE: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed 
      with tumor necrosis factor alpha and interleukin-2, designed to induce T-cell 
      infiltration and cytotoxicity in solid tumors. PATIENTS AND METHODS: TUNIMO 
      (NCT04695327) was a single-arm, multicenter phase I dose escalation trial 
      designed to assess safety of TILT-123 in advanced solid cancers refractory to 
      standard therapy. Patients received intravenous and intratumoral TILT-123. The 
      primary endpoint was safety by adverse events (AEs), laboratory values, vital 
      signs, and electrocardiograms. Secondary endpoints included tumor response, 
      pharmacokinetics, and predictive biomarkers. RESULTS: 20 patients were enrolled, 
      with median age of 58 years. Most prevalent cancer types included sarcomas (35%), 
      melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were 
      observed. The most frequent treatment related AEs included fever (16.7%), chills 
      (13.0%) and fatigue (9.3%). 10 patients were evaluable for response on day 78 
      with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET 
      was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST (20% of 
      evaluable patients). Tumor size reductions occurred in both injected and 
      non-injected lesions. TILT-123 was detected in injected and non-injected tumors, 
      and virus was observed in blood after intravenous and intratumoral injections. 
      Treatment resulted in reduction of lymphocytes in blood, with concurrent 
      lymphocyte increases in tumors, findings compatible with trafficking. 
      CONCLUSIONS: TILT-123 was safe and able to produce anti-tumor effects in local 
      and distant lesions in heavily pre-treated patients. Good tolerability of 
      TILT-123 facilitates combination studies, several of which are ongoing 
      (NCT04217473, NCT05271318, NCT05222932, NCT06125197).
FAU - Pakola, Santeri A
AU  - Pakola SA
AUID- ORCID: 0000-0001-6235-8612
AD  - University of Helsinki, Helsinki, Finland.
FAU - Peltola, Katriina J
AU  - Peltola KJ
AUID- ORCID: 0000-0002-3007-193X
AD  - Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Uusimaa, 
      Finland.
FAU - Clubb, James H A
AU  - Clubb JHA
AUID- ORCID: 0000-0002-9146-4817
AD  - University of Helsinki, Finland.
FAU - Jirovec, Elise
AU  - Jirovec E
AUID- ORCID: 0009-0004-0606-6577
AD  - University of Helsinki, Finland.
FAU - Haybout, Lyna
AU  - Haybout L
AUID- ORCID: 0009-0005-5170-5611
AD  - University of Helsinki, Helsinki, Finland.
FAU - Kudling, Tatiana V
AU  - Kudling TV
AUID- ORCID: 0000-0003-4481-1617
AD  - University of Helsinki, Helsinki, Finland.
FAU - Alanko, Tuomo
AU  - Alanko T
AUID- ORCID: 0000-0002-1649-9040
AD  - Docrates Cancer Center, Helsinki, Finland.
FAU - Korpisaari, Riitta
AU  - Korpisaari R
AUID- ORCID: 0009-0000-9924-1629
AD  - Docrates Cancer Center, Finland.
FAU - Juteau, Susanna
AU  - Juteau S
AUID- ORCID: 0000-0001-9321-2093
AD  - University of Helsinki Haartman Institute, Helsinki, Finland.
FAU - Jaakkola, Marjut
AU  - Jaakkola M
AUID- ORCID: 0000-0003-1709-3138
AD  - Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Uusimaa, 
      Finland.
FAU - Sormunen, Jorma
AU  - Sormunen J
AUID- ORCID: 0000-0002-1992-1251
AD  - Docrates Cancer Center, Helsinki, Finland.
FAU - Kemppainen, Jukka
AU  - Kemppainen J
AUID- ORCID: 0000-0001-9390-1198
AD  - Docrates Cancer Center, Finland.
FAU - Hemmes, Annabrita
AU  - Hemmes A
AUID- ORCID: 0009-0005-5051-9331
AD  - University of Helsinki, Helsinki, Finland.
FAU - Pellinen, Teijo
AU  - Pellinen T
AUID- ORCID: 0000-0001-9652-7373
AD  - University of Helsinki, Helsinki, Finland.
FAU - van der Heijden, Mirte
AU  - van der Heijden M
AUID- ORCID: 0009-0000-4123-6464
AD  - University of Helsinki, Finland.
FAU - Quixabeira, Dafne C A
AU  - Quixabeira DCA
AUID- ORCID: 0000-0003-2614-3942
AD  - University of Helsinki, Helsinki, Finland.
FAU - Kistler, Claudia
AU  - Kistler C
AUID- ORCID: 0009-0003-8445-4164
AD  - TILT Biotherapeutics Ltd, Helsinki, Finland.
FAU - Sorsa, Suvi
AU  - Sorsa S
AUID- ORCID: 0009-0002-1709-611X
AD  - University of Helsinki, Finland.
FAU - Havunen, Riikka
AU  - Havunen R
AUID- ORCID: 0009-0008-7926-5285
AD  - University of Helsinki, Finland.
FAU - Santos, Joao M
AU  - Santos JM
AUID- ORCID: 0000-0003-4639-1644
AD  - University of Helsinki, Finland.
FAU - Cervera-Carrascon, Victor
AU  - Cervera-Carrascon V
AUID- ORCID: 0000-0001-6684-3666
AD  - University of Helsinki, Helsinki, Finland.
FAU - Hemminki, Akseli E
AU  - Hemminki AE
AUID- ORCID: 0000-0001-7103-8530
AD  - University of Helsinki, Helsinki, Finland.
LA  - eng
SI  - ClinicalTrials.gov/NCT06125197
SI  - ClinicalTrials.gov/NCT05271318
SI  - ClinicalTrials.gov/NCT04217473
SI  - ClinicalTrials.gov/NCT05222932
PT  - Journal Article
DEP - 20240328
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
SB  - IM
EDAT- 2024/03/28 12:45
MHDA- 2024/03/28 12:45
CRDT- 2024/03/28 09:03
PHST- 2024/03/27 00:00 [accepted]
PHST- 2023/12/10 00:00 [received]
PHST- 2024/01/21 00:00 [revised]
PHST- 2024/03/28 12:45 [medline]
PHST- 2024/03/28 12:45 [pubmed]
PHST- 2024/03/28 09:03 [entrez]
AID - 742033 [pii]
AID - 10.1158/1078-0432.CCR-23-3874 [doi]
PST - aheadofprint
SO  - Clin Cancer Res. 2024 Mar 28. doi: 10.1158/1078-0432.CCR-23-3874.