We'd like your feedback
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Ruth
Plummer
+44 (0) 1912138444
ruth.plummer@newcastle.ac.uk
Dr
Ana
Slipicevic
+46 708555189
ana.slipicevic@one-carbon.com
Advanced solid tumors
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
This is a Phase 1a (dose escalation)/Phase Ib (dose expansion) single arm study of TH9619 in patients with selected tumor types who have been treated with available standard of care therapies. This study drug, TH9619, was tested in laboratory and animal studies and will now be tested for the first time in humans to evaluate its safety, antitumor activity and pharmacokinetics (PK) in patients. PK is an analysis of how a drug is absorbed, distributed, and eliminated from the body. A single-arm study is one in which the activities of the study drug are not compared to those of another.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
Current inclusion criteria as of 14/05/2025:
1. Willing and able to give written informed consent for participation in the study before performance of any study-specific screening procedures
2. Male or female subject aged ≥18 years of age
3. Histopathologically confirmed CRC, HNSCC, NSCLC, and gastric cancer with metastatic and/or unresectable disease (not amenable to treatment with curative intent), except for:
3.1. NSCLC with EGFR driver mutations including but not limited to del19, L858R
3.2. Gastrointestinal Stromal cell Tumors (GIST)
3.3. CRC with MSI-H
4. Treatment with at least one prior line of cytotoxic systemic therapy for metastatic/unresectable disease, including but not limited to pemetrexed, capecitabine, MTX, 5-FU, tegafur, oxaliplatin, irinotecan, cisplatin, and carboplatin
5. Prior systemic neoadjuvant or adjuvant therapy will be considered as one line of therapy if radiological progression occurred either during that treatment or within 6 months of completion
6. Progressive disease as per investigator assessment after latest given therapy
7. At least one measurable lesion by RECIST v1.160
8. Must have tumor lesion(s) or metastases amenable to biopsy, excluding bone metastases, as confirmed by a radiologist, if appropriate, and as deemed safe by the investigator
9. Mandatory pre-treatment and on-treatment biopsies (except for subjects treated at the lowest dose levels within the accelerated titration
10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
11. Life expectancy of at least 12 weeks as judged by the investigator
12. The following safety laboratory parameters must be met during screening (within 15 days) and also immediately before first IMP administration:
12.1. Total bilirubin ≤1.5 x upper limit of normal (ULN), or unconjugated bilirubin of ≤ 3 x ULN in subjects diagnosed with Gilbert’s syndrome
12.2. Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 3.0 x ULN (≤5 x ULN allowed in patients with metastases in the liver)
12.3. Renal function: Estimated creatinine clearance by eGFR ≥50 mL/min
12.4. Absolute neutrophil count (ANC) ≥1500 cells/mm³ (1.5 x 10⁹/L)
12.5. Platelet count ≥100000 cells/mm³ (100 x 10⁹/L)
12.6. Hemoglobin ≥90 g/L
12.7. Albumin levels 3.4-5.4 g/dL in the normal range of institutional standards
12.8. Folic acid levels 3.1-17.5 ng/mL (7.0-39.7 nmol/L) in the normal range of institutional standards
12.9. Vitamin B12 levels of >250 pg/mL (>185 pmol/L)
13. Contraceptive measures
13.1. Women of childbearing potential (WOCBP) must:
13.1.1. Have a negative pregnancy test within 1 week before first dose of study drug
13.1.2. Use highly effective method(s) of birth control consistently and correctly during the study and for at least 6 months after the last dose of treatment
13.1.3. Agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 6 months after the last study drug administration
13.1.4. Agree to not breastfeed and not plan to become pregnant during the study and for at least 6 months after the last study drug administration
13.2. Males who are sexually active must:
13.2.1. Agree to use a condom with spermicidal foam/gel/film/cream/suppository during the study and for at least 90 days after the last study drug administration
13.2.2. Agree to not donate sperm during the study and for at least 90 days after the last study drug administration
13.2.3. Have no plan to f
You may not be able to take part if:
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject’s ability to participate in the study2. Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of first administration of IMP, as judged by the Investigator 2.1. Any toxicities from prior treatment(s) (incl surgery, RT and systemic therapies) grade >2 by NCI CTCAE v5.0 criteria prior to first dose of study treatment 2.2. Clinically significant cardiovascular disease, defined as any of the following: 2.2.1. Major ECG abnormalities (e.g., symptomatic or sustained atrial or ventricular arrhythmias, second- or third-degree atrioventricular block, clinically significant bundle branch blocks, clinically significant ventricular hypertrophy) 2.2.2. Including dihydropyrimidine dehydrogenase polymorphisms (DDP) and fluoropyrimidine toxicity3. Primary brain malignancy or known, untreated central nervous system (CNS) or leptomeningeal metastases, or symptoms suggesting CNS involvement for which treatment is required. Screening of asymptomatic patients without history of CNS metastases is not required. Subjects with previously treated brain metastases are eligible, provided they have not experienced a seizure, had no significant change in neurological status, and have not required steroids for management of brain metastases in the last 2 weeks prior to enrollment4. Active known second malignancy with the exception of any of the following: 4.1. Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer 4.2. Adequately treated Stage 1 cancer from which the patient is currently in remission and has been in remission for ≥2 years 4.3. Low-risk prostate cancer with a Gleason score <7 and a prostate-specific antigen (PSA) level <10 ng/mL 4.4. Any other cancer from which the patient has been disease-free for ≥3 years. Malignancy (other than the one diagnosed) within the past 5 years, with the exception of any other malignancy that has been treated with no signs of relapse within 3 years (e.g., superficial melanoma, low grade cervix cancer)5. Any planned major surgery within the duration of the study (i.e., from screening to end of study visit)6. Active and uncontrolled infection requiring intravenous antibiotic or antiviral treatment within 2 weeks prior to first IMP administration7. Subjects with known active HBV (screening for HBV is not required for subjects who do not have a history of HBV, unless required by local regulations) and with treated/chronic HBV are eligible provided they meet the following criteria: 7.1. Subjects with positive HBsAg must be on permitted suppressive antiviral therapy prior to first IMP administration, remain on the same antiviral treatment throughout the study and should follow local standards for continuation of therapy after completion of IMP 7.2. Note: while HBsAg-negative, anti-HBc–positive subjects are at lower risk of HBV reactivation compared with HBsAg-positive subjects, risk of HBV reactivation should be considered in all subjects and the need for anti-HBV prophylaxis should be carefully assessed prior to the initiation of the IMP 7.3. Undetectable HBV DNA ≤ 14 days of C1D1 7.4. Note: subjects who are HBsAg positive and HBV DNA positive (detectable) will be excluded8. Known hepatitis C or human immunodeficiency virus (HIV) infection 8.1. Subjects with known positivity for HIV and who have well-controlled HIV infection/disease 8.1.1. Subject with a history of Kaposi Sarcoma and/or multicentric Castleman Disease is excluded 8.2. Subjects with known active HCV and previously treated for HCV9. Prolonged QTcF (> 450 ms), or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator10. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to TH961911. Any anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, immunotherapy) within 28 days or 5 times the half-life (whichever is shorter) before study treatment12. Planned treatment or treatment with another investigational drug within 28 days or 5 times the half-life such as other anti-cancer therapy prior to first IMP administration. Subjects consented and screened but not dosed in previous Phase 1 studies will not be excluded13. Current alcohol and/or drug abuse, as judged by the Investigator14. The Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Dr
Ana
Slipicevic
+46 708555189
ana.slipicevic@one-carbon.com
Dr
Ruth
Plummer
+44 (0) 1912138444
ruth.plummer@newcastle.ac.uk
The study is sponsored by One-carbon Therapeutics AB and funded by One-carbon Therapeutics AB.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
