TT-702 in Patients With Advanced Solid Tumours.

Recruiting now · Phase 1/Phase 2

Conditions studied: Advanced Solid Tumors

In brief

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.

Key facts

Study ID

NCT05272709

Run by

Cancer Research UK

People needed

188

Starts

2022-01-19

Expected to finish

2027-06-01

Last updated by the study team

2024-05-13

Who can join

Age: 16 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• Life expectancy estimated by the Investigator to be at least 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Cohort 1M/2M (TT-702 monotherapy) - Aged 16 years or over at the time consent is given.
• Cohort 1A/2A (TT-702 \& darolutamide combination cohorts) - Aged 18 years or over at the time consent is given.
• Haematological and biochemical indices within the protocol specified ranges.
• Objectively or measurable evaluable disease, radiologically according to RECIST Version 1.1 (and/or, in mCRPC patients, according to PCWG3 criteria). Has radiological disease progression (and/or, in mCRPC patients, PSA progression according to PCWG3 criteria) at the time of study enrolment.
• Castrate levels of testosterone (<1.7 nmol/L [50 ng/dL]) (mCRPC patients only).
• Phase I, dose escalation phase
• Histologically or cytologically proven advanced solid tumours refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the patient. Phase I dose escalation cohorts are:
• Phase I, Cohort 1M (TT-702 monotherapy cohort): Any solid tumour for which standard of care has been exhausted or, is considered inappropriate for or, declined by the patient.
• Phase I, Cohort 1A (TT-702 \& darolutamide combination cohort): mCRPC previously treated with a next generation AR antagonist (including enzalutamide, apalutamide or darolutamide) or abiraterone.
• Phase I, Cohort 1P (TT-702 \& PD-1/PD-L1 combination cohort): Patients with PD-1/PD-L1 resistant tumours (i.e. disease progression after a prior PD-1/PD-L1 inhibitor with at least 12 weeks treatment).
• Phase II (expansion phase)
• Histologically or cytologically proven advanced solid tumour of particular interest based on preclinical and clinical data, refractory to conventional treatment or, for which no conventional therapy is considered appropriate by the Investigator or, is declined by the patient. Phase II expansion cohorts are:
• Cohort 2M (TT-702 Monotherapy expansion cohorts) - mCRPC,TNBC and MMR/MSI defective tumours:
• MMR/MSI defective tumours:
• Prior treatment with an anti-PD-1 or anti-PD-L1 agent, either as monotherapy or in combination with other agent(s). This should be the preceding treatment prior to trial entry.
• Patients must have progressed on an anti-PD-1/anti-PD-L1 agent.
• Patients must have experienced Investigator-assessed initial clinical benefit from the most recent anti-PD-1/anti-PD-L1 treatment (either as monotherapy or in combination with other compounds) for at least 10 weeks. Initial benefit is defined as SD or better with an anti-PD 1/anti-PD-L1 therapy.
• Diagnosis of metastatic MSI-H (defined as MSI polymerase chain reaction test with instability shown in ≥2 or ≥30% of microsatellite markers) or metastatic MMRd (defined as loss of MLH1, MSH2, MSH6, and/or PMS2 expression is detected) through local testing in NHS lab within UKAS/ISO 15198 scope of accreditation.
• mCRPC:

You may not qualify if…

• 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.
• Cohort 1M/2M (monotherapy) - Women of childbearing potential (or are already pregnant or lactating). However, those patients who meet the following points are considered eligible:
• Have a negative highly sensitive pregnancy test of a serum sample within 7 days prior to trial inclusion; and
• Agree to use two forms of medically approved contraception: i. one highly effective form including but not limited to: oral, injected,implanted, transdermal or intravaginal hormonal contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormonereleasing system, bilateral tubal occlusion or vasectomised partner; ii. plus a barrier method (for example, condom plus spermicide); iii. or agree to sexual abstinence. Effective from the first administration of TT-702, throughout the trial and for six months after the last administration of IMP.
• Male patients with partners of childbearing potential. However, those patients who meet the following points are considered 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.
• Male patients with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicide) to prevent exposure of the foetus or neonate.
• 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.
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection. Patients with previous Hepatitis C exposure but no current infection are eligible to participate.
• Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
• Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.
• Concurrent congestive heart failure, prior history of class II-IV cardiac disease (New York Heart Association [NYHA]), prior history of clinically significant cardiac ischaemia or prior history of clinically significant cardiac arrhythmia. Patients with significant cardiovascular disease are excluded as defined by:
• History of congestive heart failure requiring therapy (NYHA III or IV);
• History of unstable angina pectoris or myocardial infarction up to six months prior to trial entry (patients with previous cardiac or thrombotic events who are now stable and or recovered are eligible);
• Presence of severe valvular heart disease;
• Presence of a ventricular arrhythmia requiring treatment;
• Left ventricular ejection fraction < 50%;
• Has a QTcF prolongation to >470 milliseconds (ms) based on a 12-lead ECG in triplicate;
• Previous stroke or transient ischaemic attack within 6 months of trial entry;
• History of clinically significant peripheral vascular disease/vasculitis/vasculopathy;
• Cohort 1A/2A - A history of QTcF prolongation or Torsade de pointes.
• Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I/II trial of TT-702. Participation in an observational trial or interventional clinical trial which does not involve administration of an IMP and which would not place an unacceptable burden on the patient in the opinion of the Investigator would be acceptable.

Where it is running

• Royal Marsden Hospital NHS Foundation Trust — London, United Kingdom (enrolling)
• The Christie NHS Foundation Trust — Manchester, United Kingdom (enrolling)
• University Hospital Southampton NHS Foundation Trust — Southampton, United Kingdom (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.