Study of safety, pharmacokinetics, and anti-tumor activity of GTAEXS617 in patients with advanced solid tumors.
- Conditions
- advanced solid tumorsMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10006204Term: Breast carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10061328Term: Ovarian epithelial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10052360Term: Colorectal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10051971Term: Pancreatic adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-003475-42-BE
- Lead Sponsor
- Exscientia AI Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 177
1. Aged =18 years at the time of signing the informed consent.
2. Able and willing to provide written informed consent prior to start of any study-specific procedures.
3. ECOG performance status 0-1.
4. Estimated life expectancy >3 months.
5. Ability to swallow and retain oral medication.
6. One the following histologically or cytologically confirmed advanced solid tumors: head and neck squamous adenocarcinoma, colorectal adenocarcinoma, pancreatic adenocarcinoma, NSCLC, breast carcinoma (HR+ and HER2- that has progressed to a prior treatment with CD4/CDK6 inhibitor), or ovarian epithelial carcinoma.
7. a) Applicable to combination parts: Advanced disease (ie, not eligible for curative surgery or radiotherapy), recurrent, or metastatic in patients who have failed SoC therapies. Patients who have been offered SoC therapies and refused (must be documented) may be eligible on discussion with the Sponsor.
b) Applicable to monotherapy parts: Advanced disease (ie, not eligible for curative surgery or radiotherapy), recurrent, or metastatic in patients who have failed or are ineligible for SoC therapies. Patients who have been offered SoC therapies and refused (must be documented), or who are considered ineligible for these, may be eligible on discussion with the Sponsor.
8. Adequate hematological, liver, and renal function defined below (repeated measurements of borderline values are permitted once):
o Hemoglobin =8.5 g/dL. Any red blood count transfusion must have occurred at least 28 days prior to Screening.
o Absolute neutrophil count =1.5 × 109/L. Any granulocyte colony-stimulating factor transfusion must have occurred at least 21 days prior to Screening.
o Platelet count =100 × 109/L. Any platelet transfusion must have occurred at least 7 days prior to Screening.
o Total bilirubin =1.5 institutional ULN, (or where =2 × ULN with known hepatobiliary metastases or =3 × ULN if known Gilbert’s syndrome).
o ALT or AST =3 × ULN (or =5 × ULN if liver metastases are present).
o Serum creatinine <1.5 × ULN.
9. Female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
o Not a woman of childbearing potential (WOCBP) (as defined in Appendix 2 of the protocol).
OR
o A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 of the protocol during the treatment period and for at least 6 months after the final dose of study treatment.
10. A nonsterilized male participant with female partners of reproductive potential must agree to use contraception during the treatment period and for at least 6 months after the final dose of the study treatment and must refrain from donating sperm during this period. Acceptable methods of contraception are defined in Appendix 2 of the protocol.
11. Participant 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 53
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 124
1. Any medical or psychiatric condition that, in the view of the Investigator, could jeopardize or would compromise the participant’s safety or ability to participate in the study and make them unsuitable for participation
2. Known hypersensitivity to any components of the study treatment or comparable drugs (drugs targeting CDK7)
3. Active and clinically significant infection requiring systemic antibacterial, antiviral, or antifungal therapy =7 days of the first scheduled dose of the study treatment
4. Known active infections with hepatitis B, hepatitis C, known human immunodeficiency virus, or acquired immunodeficiency syndrome related illness
5. Refractory nausea and/or vomiting, chronic gastrointestinal disease, or previous significant bowel resection, with CS sequelae that would preclude adequate absorption of GTAEXS617
6. Symptomatic CNS malignancy or metastases. Participants with asymptomatic CNS lesions should have completed standard therapy for their CNS lesions 30 days prior to study enrollment, and all radiation related toxicities, except alopecia, have resolved to Grade 1 or less and participant is on stable (non-tapering) dose of steroids
7. Concurrent active or previous malignancy (other than the primary malignancy for which the participant will be treated on this protocol – except for full resected squamous cell carcinoma of the skin, cervical carcinoma in situ or basal cell carcinoma) that could interfere with response evaluation
8. Prior organ or allogeneic stem-cell transplantation
9. Moderate or severe cardiovascular disease
o Presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
o Documented major ECG abnormalities at the Investigator’s discretion
o Participant has experienced any of the following during the last 6 months: coronary/peripheral bypass graft, cerebrovascular accident, transient ischemic attack, deep vein thrombosis, or symptomatic pulmonary embolism
10. Received medications known to prolong QTc within 5 half-lives before the first dose of the study treatment
11. QTcF >480 msec or history of torsades de pointes or history of congenital long QT syndrome. Patients with an apparent prolonged QT due to bundle branch block may be eligible on discussion with the Sponsor
12. Administration of a live vaccine within 28 days of starting study treatment and for up to 1 month after the final dose of study treatment or anticipation that such vaccine will be required during the study. Note: mRNA-based vaccines for COVID-19 and inactivated flu vaccines are allowed
13. Received anticancer therapy, including chemotherapy, immunotherapy, radiation therapy (with the exception of palliative radiotherapy), biologic therapy, cancer-related hormonal therapy, or any investigational therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of the study treatment
14. Received treatment with known strong inhibitors and or inducers of CYP3A within 14 days or 5 half-lives of the CYP3A modulator (whichever is longer) before the first dose of study treatment. Participants who have received moderate CYP3A inhibitors or inducers may be accepted onto the study at the discretion of the Investigator and on agreement with the Sponsor
15. Participants who have received treatment with known inhibitors or inducers of P-glycoprotein or breast cancer res
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method