About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Be able to provide informed consent and be capable of co-operating with IMP administration, procedures and follow-up.
Be willing to provide samples (blood and tissue) as required.
Consent to access any available archival tissue.
Consent for fresh tumour biopsy samples at baseline and on trial (may be Investigator mandated for patients in the dose escalation phase; mandatory for a minimum of eight patients in each expansion cohort). Investigators will consider whether a biopsy is feasible for the patient in the dose escalation phase and this will not impede participation in the trial if biopsy is not a suitable option.
Disqualifiers
Radiotherapy (except single fractions for palliative reasons), endocrine therapy during the previous four weeks, immunotherapy and chemotherapy during the previous four weeks(previous six weeks for nitrosoureas, Mitomycin-C) before receiving TT-702. A washout period of eight weeks is required for enzalutamide and apalutamide before the patient receives their first dose of TT-702. A washout period of 4 weeks or 5 half-lives whichever is shorter for any other previous preceding IMPs is required before the patient receives their first dose of TT-702 (in the combination cohorts no washout is needed from PD-1/PD-L1 and darolutamide, respectively).
Patients with ongoing toxic manifestations of previous treatments greater than NCI CTCAE Version 5.0 Grade 1. Exceptions to this are alopecia and any ongoing toxic manifestation which in the opinion of the Investigator should not exclude the patient.
Patients with symptomatic brain or leptomeningeal metastases should be excluded. Asymptomatic patients with previously treated and stable brain metastases (in previous four weeks to study entry) and not requiring any steroids are eligible for the trial. Patients who are stable on anticonvulsants are also eligible.
Agree to take measures not to father children by using a barrier method of contraception [condom plus spermicide] or sexual abstinence12 effective from the first administration of IMP throughout the trial and for six months after the last administration of IMP.
Trial design
Sequential
Treatments tested in this trial
TT-702
DrugTT-702 will be administered orally, once daily, for up to 12 months.
Darolutamide
DrugDarolutamide will be administered orally, twice daily, for up to 12 months.
Treatment groups
6
Treatment groupsSee each treatment group below.
Trial outcomes
Primary outcomes
Maximum Tolerated Dose (MTD) (Dose Escalation Phase)
Determine a dose that is deemed tolerable with a target dose limiting toxicity (DLT).
Recommended Phase 2 Dose (RP2D) (Dose Escalation Phase)
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)
Graded according to National Cancer Institute Common Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Number of Grade 3, 4 and 5 TEAEs by Arm (Dose Escalation Phase)
Graded according to NCI CTCAE Version 5.0.
Secondary outcomes
Measurement of Maximum (or Peak) Plasma Concentration (Cmax) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase)
Measurement of Cmax of TT-702 and its active product TT-478 as appropriate.
Measurement of Minimal Plasma Concentration (Cmin) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase)
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)
Measurement of Tmax of TT-702 and its active product TT-478 as appropriate.
Area Under the Curve (AUC) of TT-702 and its Active Product TT-478 as Appropriate (Dose Escalation and Expansion Phase)
AUC of TT-702 and its active product TT-478 as appropriate.
Sponsors and contacts
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Cancer Research UK
Lead sponsor
Teon Therapeutics, Inc.
Collaborator