TT-702 in Patients With Advanced Solid Tumours.
- Registration Number
- NCT05272709
- Lead Sponsor
- Cancer Research UK
- Brief Summary
This clinical trial is evaluating the drug candidate TT-702 in patients with advanced solid tumours. The main aims of the trial are to determine the maximum dose of TT-702 that can be given safely to patients alone and in combination with other anti-cancer agents.
- Detailed Description
TT-702 is a 'small molecule prodrug'. TT-702 is converted into TT-478, which then targets and blocks the function of the 'A2B adenosine receptor'. It is hoped that by blocking this receptor the immune system will become more active in recognising and removing tumour cells.
This clinical trial has two phases:
* Phase I, dose escalation phase - groups of patients will receive increasing doses of TT-702 to find an optimal dose that best targets the tumours. This phase will consist of both monotherapy and combination escalation cohorts. In the combination escalation cohorts, TT-702 will be evaluated in combination with the androgen receptor (AR) antagonist darolutamide to be assessed in mCRPC. Potential agents for further combination escalation cohorts have not yet been defined.
* Phase II, expansion phase - larger groups of patients will receive the selected dose of TT-702 considered to be optimal in the Phase I, dose escalation phase. This phase will consist of three monotherapy expansion cohorts (metastatic castrate resistant prostate cancer \[mCRPC\] cohort, Mismatch Repair \[MMR\]/ Microsatellite Instability \[MSI\] defective tumours cohort and a triple negative breast cancer \[TNBC\] cohort) and combination expansion cohorts. In the combination expansion cohorts, TT-702 will be evaluated in combination with the androgen receptor (AR) antagonist darolutamide to be assessed in mCRPC. Potential agents for further combination expansion cohorts have not yet been defined.
The main aims of this trial are to:
* Find the maximum dose of TT-702 as a monotherapy and in combination with other anti-cancer drugs that can be given safely to patients.
* Define the side effects of TT-702 and how these can be managed.
* Determine the pharmacokinetics (PK) and elimination kinetics of TT-702.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 188
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1M (Monotherapy escalation cohort) TT-702 This cohort will recruit patients with solid tumours. Cohort 2M: TNBC (Monotherapy expansion cohort) TT-702 This cohort will recruit patients with TNBC only. Cohort 2M: MSI/MMR defective tumours (Monotherapy expansion cohort) TT-702 This cohort will recruit patients with MSI/MMR defective tumours only. Cohort 2M: mCRPC (Monotherapy expansion cohort) TT-702 This cohort will recruit patients with mCRPC only. Cohort 1A (TT-702 + Darolutamide combination escalation cohort) TT-702 This cohort will recruit patients with mCRPC only. Cohort 2A (TT-702 + Darolutamide combination expansion cohort) TT-702 This cohort will recruit patients with mCRPC only. Cohort 1A (TT-702 + Darolutamide combination escalation cohort) Darolutamide This cohort will recruit patients with mCRPC only. Cohort 2A (TT-702 + Darolutamide combination expansion cohort) Darolutamide This cohort will recruit patients with mCRPC only.
- Primary Outcome Measures
Name Time Method Assess Number of Patients with Confirmed Complete Response (CR) and Partial Response (PR) (MSI/MMR and TNBC Arms Expansion Phase) Radiological assessment within 28 days before starting TT-702; end of every 3 cycles (21-day cycles) up to 6 months then every 4 cycles & treatment discontinuation and/or off-study visit (max. 13 months) The number of patients who have a confirmed CR or PR according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1.
Assess Number of Patients with Confirmed CR and PR (mCRPC Arms Expansion Phase) Radiological assessment (CT/MRI) within 28 days & bone scan (if required) within 8 weeks before starting TT-702; end of every 3 cycles (21-day cycles) up to 6 months then every 4 cycles & treatment discontinuation and/or off-study visit (max. 13 months) The number of patients who have a confirmed CR or PR according to Prostate Cancer Working Group 3 criteria (PCWG3) (encompassing RECIST 1.1 and Prostate Specific Antigen \[PSA\] level changes) in patients with mCRPC.
Maximum Tolerated Dose (MTD) (Dose Escalation Phase) Cycle 0 Day 1 to Cycle 2 Day 1 Determine a dose that is deemed tolerable with a target dose limiting toxicity (DLT).
Recommended Phase 2 Dose (RP2D) (Dose Escalation Phase) Cycle 0 Day 1 to off-study visit (max. 13 months) The RP2D will be determined after reviewing all of the clinically relevant toxicity, efficacy and pharmacokinetic/pharmacodynamic data by the Trial Management Group.
Number of Treatment-Emergent Adverse Events (TEAEs) by Arm (Dose Escalation Phase) Safety data will be collected from the time of informed consent until 21 days after the last dose of TT-702. The average time from consent to the end of follow up will be presented. Graded according to National Cancer Institute Common Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Number of TEAEs Related to TT-702 and/or Darolutamide by Arm (Dose Escalation Phase) Safety data will be collected from the time of informed consent until 21 days after the last dose of TT-702. The average time from consent to the end of follow up will be presented. Graded according to NCI CTCAE Version 5.0.
Number of Grade 3, 4 and 5 TEAEs by Arm (Dose Escalation Phase) Safety data will be collected from the time of informed consent until 21 days after the last dose of TT-702. The average time from consent to the end of follow up will be presented. Graded according to NCI CTCAE Version 5.0.
- Secondary Outcome Measures
Name Time Method Assess Number of Patients with Confirmed CR and PR (Dose Escalation Phase). Radiological assessment (CT/MRI) within 28 days & bone scan (if required) within 8 weeks before starting TT-702; end of every 3 cycles (21-day cycles) up to 6 months then every 4 cycles & treatment discontinuation and/or off-study visit (max. 13 months). The number of patients who have a confirmed CR or PR according to RECIST Version 1.1 or according to PCWG3 criteria (encompassing RECIST 1.1 and PSA level changes) in patients with mCRPC.
Duration of Response and of Clinical Benefit Defined as Duration of Confirmed CR, PR or Stable Disease (SD) (Dose Escalation and Expansion Phase) Radiological assessment (CT/MRI) within 28 days & bone scan (if required) within 8 weeks before starting TT-702; end of every 3 cycles (21-day cycles) up to 6 months then every 4 cycles & treatment discontinuation and/or off-study visit (max. 13 months). The duration of CR, PR or SD according to RECIST Version 1.1 or according to PCWG3 criteria (encompassing RECIST 1.1 and PSA level changes) in patients with mCRPC.
Number of Patients who are still Alive at 12 Months (Dose Escalation and Expansion Phase) From first dose of TT-702 until 12 months after first dose of TT-702 Number of patients who are still alive at 12 months.
Number of Patients whose Cancer has not Progressed at Six Months (Dose Escalation and Expansion Phase ) From first dose of TT-702 until six months after first dose of TT-702 Number of patients whose cancer has not progressed at six months.
Number of Treatment-Emergent Adverse Events (TEAEs) by Arm (Dose Expansion Phase). Safety data will be collected from the time of informed consent until 21 days after the last dose of TT-702. The average time from consent to the end of follow up will be presented Graded according to NCI CTCAE version 5.0.
Number of Grade 3, 4 and 5 TEAEs by Arm (Dose Expansion Phase). Safety data will be collected from the time of informed consent until 21 days after the last dose of TT-702. The average time from consent to the end of follow up will be presented Graded according to NCI CTCAE version 5.0.
Area Under the Curve (AUC) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase) From first dose of TT-702 until discontinuation visit (max. 12 months) AUC of TT-702 and its active product TT-478 as appropriate.
Apparent Clearance of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase) From first dose of TT-702 until discontinuation visit (max. 12 months) Apparent clearance of TT-702 and its active product TT-478 as appropriate.
Volume of Distribution of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase) From first dose of TT-702 until discontinuation visit (max. 12 months) Volume of Distribution of TT-702 and its active product TT-478 as appropriate.
Assess Number of Patients with Confirmed CR and PR after 3, 6, 9 and 12 Cycles and at Any Time while on Trial (Dose Escalation and Expansion Phase) Radiological assessment (CT/MRI) within 28 days & bone scan (if required) within 8 weeks before starting TT-702; end of every 3 cycles (21-day cycles) up to 6 months then every 4 cycles & treatment discontinuation and/or off-study visit (max. 13 months). The number of patients who have a confirmed CR or PR according to RECIST Version 1.1 or according to PCWG3 criteria (encompassing RECIST 1.1 and PSA level changes) in patients with mCRPC after 3, 6, 9 and 12 cycles and at any time while on trial.
Number of TEAEs Related to TT-702 and/or Darolutamide by Arm (Dose Expansion Phase) Safety data will be collected from the time of informed consent until 21 days after the last dose of TT-702. The average time from consent to the end of follow up will be presented Graded according to NCI CTCAE version 5.0.
Measurement of Minimal Plasma Concentration (Cmin) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase) From first dose of TT-702 until discontinuation visit (max. 12 months) Measurement of Cmin of TT-702 and its active product TT-478 as appropriate.
Measurement of Time at Cmax (Tmax) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase) From first dose of TT-702 until discontinuation visit (max. 12 months) Measurement of Tmax of TT-702 and its active product TT-478 as appropriate.
Measurement of Maximum (or Peak) Plasma Concentration (Cmax) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase) From first dose of TT-702 until discontinuation visit (max. 12 months) Measurement of Cmax of TT-702 and its active product TT-478 as appropriate.
Terminal Elimination Half-Life (T1/2) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase) From first dose of TT-702 until discontinuation visit (max. 12 months) T1/2 of TT-702 and its active product TT-478 as appropriate.
Trial Locations
- Locations (3)
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Royal Marsden Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom