TT-702 in Patients With Advanced Solid Tumours.

NCT05272709 | Recruiting Phase 1

• 2 other identifiers: CRUKD/21/0052021-001062-37
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumors

Keywords

Adenosine receptors; MSI Deficient Cancers; MMR Deficient Cancer; Castrate resistant Prostate Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (7)

• Maximum Tolerated Dose (MTD) (Dose Escalation Phase)

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

  Cycle 0 Day 1 to Cycle 2 Day 1

• 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.

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

• 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.

  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.

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

  Graded according to NCI CTCAE Version 5.0.

  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.

• Number of TEAEs Related to TT-702 and/or Darolutamide by Arm (Dose Escalation Phase)

  Graded according to NCI CTCAE Version 5.0.

  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.

• Assess Number of Patients with Confirmed Complete Response (CR) and Partial Response (PR) (MSI/MMR and TNBC Arms Expansion Phase)

  The number of patients who have a confirmed CR or PR according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1.

  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)

• Assess Number of Patients with Confirmed CR and PR (mCRPC Arms Expansion Phase)

  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.

  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)

Secondary Outcomes (15)

• 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 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 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)

• 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)

• 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)

Study Arms (6)

Cohort 1M (Monotherapy escalation cohort)

EXPERIMENTAL

This cohort will recruit patients with solid tumours.

Drug: TT-702

Cohort 2M: mCRPC (Monotherapy expansion cohort)

EXPERIMENTAL

This cohort will recruit patients with mCRPC only.

Drug: TT-702

Cohort 2M: MSI/MMR defective tumours (Monotherapy expansion cohort)

EXPERIMENTAL

This cohort will recruit patients with MSI/MMR defective tumours only.

Drug: TT-702

Cohort 2M: TNBC (Monotherapy expansion cohort)

EXPERIMENTAL

This cohort will recruit patients with TNBC only.

Drug: TT-702

Cohort 1A (TT-702 + Darolutamide combination escalation cohort)

EXPERIMENTAL

This cohort will recruit patients with mCRPC only.

Drug: TT-702; Drug: Darolutamide

Cohort 2A (TT-702 + Darolutamide combination expansion cohort)

EXPERIMENTAL

This cohort will recruit patients with mCRPC only.

Drug: TT-702; Drug: Darolutamide

Interventions

TT-702 DRUG

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

Cohort 1A (TT-702 + Darolutamide combination escalation cohort); Cohort 1M (Monotherapy escalation cohort); Cohort 2A (TT-702 + Darolutamide combination expansion cohort); Cohort 2M: MSI/MMR defective tumours (Monotherapy expansion cohort); Cohort 2M: TNBC (Monotherapy expansion cohort); Cohort 2M: mCRPC (Monotherapy expansion cohort)

Darolutamide DRUG

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

Cohort 1A (TT-702 + Darolutamide combination escalation cohort); Cohort 2A (TT-702 + Darolutamide combination expansion cohort)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

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:
• 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);

Sponsors & Collaborators

• Cancer Research UK: lead
• Teon Therapeutics, Inc.: collaborator

Study Sites (3)

Royal Marsden Hospital NHS Foundation Trust

London, SM2 5PT, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

RECRUITING

Related Publications (1)

• Whitaker D, Francis L, Karaborni S, Smith S, Craigen JL, Svetlik S, Barnett S, Veal GJ. Development and validation of an LC-MS/MS method for the quantification of novel therapeutic TT-478, a selective adenosine receptor 2B antagonist, for a phase I/II clinical trial. Bioanalysis. 2025 Sep;17(17):1105-1112. doi: 10.1080/17576180.2025.2554564. Epub 2025 Oct 17.

  PMID: 41104540 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

darolutamide

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Johann de Bono, Prof

  The Royal Marsden Hospital/ The Institute of Cancer Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Johann de Bono, Prof

CONTACT

+44 (0)208 722 4029; Johann.debono@icr.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 9, 2022
• Study Start: January 19, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)