TT-702 in Patients With Advanced Solid Tumours.
ConditionAdvanced Solid Tumors
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 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. 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 (no washout is needed from ICI).
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 trial entry) and not requiring any steroids are eligible for the trial. Patients who are stable on anticonvulsants are also eligible.
Non-vasectomised male patients must also be willing to ensure that any partner of childbearing potential uses a highly effective method of contraception (for example, oral, injected, implanted, transdermal or intravaginal hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system or bilateral tubal occlusion) or agree to sexual abstinence for the same duration.
Trial design
Design model
Sequential
Treatments tested in this trial
TT-702
DrugTT-702 will be administered orally, once daily, for up to 12 months.
Anti-PD-1 and PD-L1 agent
DrugAn appropriate anti-PD-1/PD-L1 combination agent will be selected and implemented following a substantial amendment.
Treatment groups
60 Participants
are divided into 4 treatment groupsGroup A: Cohort 1M (Monotherapy escalation cohort)Experimental treatment 1 intervention
Group B: Cohort 2M: (Monotherapy expansion cohort)Experimental treatment 1 intervention
Group C: Cohort 1P (Combination escalation cohort)Experimental treatment 1 intervention
Group D: Cohort 2P (Combination expansion cohort)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Number of Dose Limiting Toxicities (DLTs) (Dose Escalation Phase)
Dose Limiting Toxicities to TT-702 are determined by testing increasing doses of TT-702 administered once daily in continuous 21-day cycles in escalation cohorts. Dose limiting toxicities are defined per protocol as a highly probably or probably TT-702-related adverse events (AEs) of neutropenia, thrombocytopenia, non-haematological toxicities, photosensitivity, death or other drug-related toxicity causing TT-702 interruption, occurring during Cycle 0 or Cycle 1 administration.
Time frame
From the first dose in Cycle 0, until completion of Cycle 1 (3 weeks [+ 3-9 days to account for initial pharmacokinetic (PK) profiling period following the Cycle 0 dose]).2
Number of Treatment-Emergent AEs (TEAEs), Related TEAEs and Grade 3, 4 or 5 TEAEs (Dose Escalation Phase)
Number of TEAEs, TEAEs related to TT-702 and Grade 3, 4 or 5 TEAEs in the dose escalation phase. AEs are categorised according to Medical Dictionary for Regulatory Activities (MedDRA) and graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) versions applicable at time of reporting. AEs are assessed by the reporting study doctors for a causal relationship to TT-702. Related are those AEs with a causality of possible, probable or highly probable. All AEs are collected until the off-study visit, approximately 21 (±7) days after the final dose of TT-702 and TT-702-related AEs present at the off-study visit are to be followed up monthly until resolution, return to baseline, stabilisation or initiation of another anti-cancer treatment.
Time frame
From the time of first dose until the end of the safety follow-up period for TT-702.3
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) at 6 months (Expansion Phase) and is used to assess antitumour activity according to PCWG3 or RECIST v1.1 criteria. Responses must be confirmed by repeat assessment ≥4 weeks after initial response criteria are met.
Time frame
From the first dose and until the final radiological disease assessment at the off-study visit.4
Number and Percentage of Participants that Achieved Clinical Benefit Assessed by PCWG3 and RECIST v1.1 (Expansion Phase)
Antitumour activity measured according to PCWG3 and RECIST version 1.1. Complete Response or PR/remission is confirmed by repeat measurements ≥4 weeks after response criteria are met; participants with SD are to meet criteria at least once ≥6 weeks after first dose of TT-702. Clinical Benefit Rate is defined as the proportion of participants with absence of disease progression (i.e. confirmed CR, PR or SD) for at least 24 weeks from the start of trial treatment.
Time frame
From the first dose and until the final radiological disease assessment at the off-study visit.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)
Pharmacokinetic parameters are derived from analysing the concentration of TT-702 and its active metabolite, TT-478, in plasma via Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS).
Time frame
From the first dose of TT-702 until the 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)
Pharmacokinetic parameters are derived from analysing the concentration of TT-702 and its active metabolite, TT-478, in plasma via LC-MS/MS.
Time frame
From the first dose of TT-702 until the 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)
Pharmacokinetic parameters are derived from analysing the concentration of TT-702 and its active metabolite, TT-478, in plasma via LC-MS/MS.
Time frame
From the first dose of TT-702 until the 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)
Pharmacokinetic parameters are derived from analysing the concentration of TT-702 and its active metabolite, TT-478, in plasma via LC-MS/MS.
Time frame
From the first dose of TT-702 until the discontinuation visit (max 12 months).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Cancer Research UK
Lead sponsor
Teon Therapeutics, Inc.
Collaborator
Source ClinicalTrials.gov