advanced solid tumors MedDRA version: 21.0 Level: PT Classification code 10052360 Term: Colorectal adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10051971 Term: Pancreatic adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer
Conditions
Interventions
Product Name: GTAEXS617
Product Code: GTAEXS617
Pharmaceutical Form: Tablet
INN or Proposed INN: Not yet assigned
Current Sponsor code: GTAEXS617
Other descriptive name: GTAEXS617
Concentration unit:
Sponsors
Exscientia AI Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 124
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objectives: Module 1A To characterize the safety profile of GTAEXS617 as monotherapy To establish the RP2D of GTAEXS617 as monotherapy. The RP2D will not exceed the MTD if established Module 1B To characterize the safety profile of GTSEXS617 in combination with selected SoC regimens Module 2A To evaluate the preliminary anti-tumor activity of GTAEXS617 To further evaluate the safety, tolerability, and treatment adherence of GTAEXS617 Module 2B To evaluate the preliminary anti-tumor activity of GTAEXS617 in combination with SoC To further evaluate the safety, tolerability, and treatment adherence of GTAEXS617 in combination with SoC;Secondary Objective: Module 1A To characterize the PK of GTAEXS617 following oral administration of GTAEXS617 as monotherapy in participants with advanced solid tumors Module 1B To characterize the PK of GTAEXS617 following oral administration of GTAEXS617 in combination with SoC in participants with advanced solid tumors Module 2A To further evaluate the PK of GTAEXS617 Module 2B To further evaluate the PK of GTAEXS617;Primary end point(s): Module 1A Incidence of DLTs during Cycle 1 of treatment with GTAEXS617 Incidence and severity of TEAEs; safety parameters variations from baseline Tolerability - Frequency of dose interruptions, dose reductions and dose intensity achieved Adherence – treatment diary Module 1B Incidence of DLTs during Cycle 1 of treatment with GTAEXS617 in combination with SoC Incidence and severity of TEAEs; safety parameters variations from baseline Tolerability - Frequency of dose interruptions, dose reductions and dose intensity achieved Adherence – treatment diary Module 2A ORR assessed using RECIST v1.1 Safety - Incidence and severity of TEAEs; safety parameters variations from baseline Tolerability - Frequency of dose interruptions, dose reductions and dose intensity achieved Adherence – treatment diary Module 2B ORR assessed using RECIST v1.1 Safety - Incidence and severity of TEAEs; sa | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Module 1A Plasma and urine GTAEXS617 PK parameters including but not limited to: o Cmax, tmax, AUC(0-last), AUC(0-inf), AUC(0-tau), accumulation of Cmax (RCmax) and AUC(0-tau) (RAUC(0-tau)), t1/2, CL/F, and Vz/F o By-interval and cumulative GTAEXS617 excretion in urine (Ae and fe), and CLr Module 1B Plasma GTAEXS617 PK parameters including but not limited to: o Cmax, tmax, AUC(0-last), AUC(0-inf), AUC(0-tau), accumulation of Cmax (RCmax) and AUC(0-tau) (RAUC(0-tau)), t1/2, CL/F, and Vz/F Module 2A Plasma GTAEXS617 PK concentrations and, if appropriate, plasma PK parameters Module 2B Plasma GTAEXS617 PK concentrations and, if appropriate, plasma PK parameters;Timepoint(s) of evaluation of this end point: Plasma GTAEXS617 PK parameters Module 1 Module 2 (Serial blood collections may be conducted in a subset of Module 2 participants after review of the emerging PK data from Module 1) Cycle 1: D1 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h), D2 (24h), D8 (pre-dose), D15 (pre-dose), D22 (pre-dose), Cycle 2: D1 (pre-dose, 0.5h, 1h, 2h, 4h, 6h, 8h), D2 (24h), D22 (pre-dose), Cycle 3-6: D1 (pre-dose), end of treatment Urine GTAEXS617 PK parameters Module 1 Only cycle 1: D1 (pre-dose, 0-4 h, 4-8 h), D2, cycle 2: D1 (pre-dose, 0-4 h, 4-8 h), D2 | — |
Countries
Belgium, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Exscientia AI Ltd
Outcome results
None listed