TT-702 in Patients With Advanced Solid Tumours.

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age16+
SponsorCancer Research UK

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 volunteers

Qualifiers

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

Design model

Sequential

Treatments tested in this trial

  • TT-702

    Drug

    TT-702 will be administered orally, once daily, for up to 12 months.

  • Darolutamide

    Drug

    Darolutamide will be administered orally, twice daily, for up to 12 months.

Treatment groups

188 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Cohort 1M (Monotherapy escalation cohort)Experimental treatment 1 intervention
Group B: Cohort 2M: mCRPC (Monotherapy expansion cohort)Experimental treatment 1 intervention
Group C: Cohort 2M: MSI/MMR defective tumours (Monotherapy expansion cohort)Experimental treatment 1 intervention
Group D: Cohort 2M: TNBC (Monotherapy expansion cohort)Experimental treatment 1 intervention
Group E: Cohort 1A (TT-702 + Darolutamide combination escalation cohort)Experimental treatment 2 interventions
Group F: Cohort 2A (TT-702 + Darolutamide combination expansion cohort)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Maximum Tolerated Dose (MTD) (Dose Escalation Phase)

Determine a dose that is deemed tolerable with a target dose limiting toxicity (DLT).

Time frame
Cycle 0 Day 1 to Cycle 2 Day 1
2

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.

Time frame
Cycle 0 Day 1 to off-study visit (max. 13 months)
3

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.

Time frame
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.
4

Number of Grade 3, 4 and 5 TEAEs by Arm (Dose Escalation Phase)

Graded according to NCI CTCAE Version 5.0.

Time frame
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.

Secondary outcomes

1

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.

Time frame
From first dose of TT-702 until discontinuation visit (max. 12 months)
2

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.

Time frame
From first dose of TT-702 until discontinuation visit (max. 12 months)
3

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.

Time frame
From first dose of TT-702 until discontinuation visit (max. 12 months)
4

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.

Time frame
From first dose of TT-702 until discontinuation visit (max. 12 months)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Cancer Research UK

Lead sponsor

Teon Therapeutics, Inc.

Collaborator