A Cancer Research UK Phase I/IIa clinical trial of BT1718, (A Bicycle drug conjugate) given intravenously in patients with advanced solid tumours

Cancer Research UK0 sites66 target enrollmentDecember 18, 2023

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: Cancer Research UK
Enrollment: 66
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

December 18, 2023

End Date

November 20, 2023

Last Updated

2 years ago

Study Type

Interventional

Sex

All

Investigators

Sponsor

Cancer Research UK

Eligibility Criteria

Inclusion Criteria

•1\. Written (signed and dated) informed consent and be capable of co\-operating with treatment and follow\-up
•2\. Phase I, dose\-escalation phase (Stages 1 and 2\):
•2\.1\. Histologically or cytologically proven advanced solid tumour, refractory to conventional treatment, or for which no conventional therapy is considered appropriate by the Investigator or is declined by the patient.
•Phase IIa, expansion phase:
•2\.2\. Histologically or cytologically proven advanced solid tumour of particular interest based on pre\-clinical 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 IIa expansion cohorts will be:
•2\.2\.3\. Squamous NSCLC cohort \- retrospective MT1\-MMP testing.
•2\.2\.4\. Basket cohort (advanced solid tumours, excluding patients eligible for one of the other recruiting expansion cohorts) \- high MT1\-MMP expression by IHC assay using archival tumour sample (mandatory fresh tumour samples for those patients without available archival tumour samples or additional analysis is deemed necessary). Retrospective testing may be permitted for tumour types estimated to have high MT1\-MMP positivity rates as per the Laboratory manual.
•2\.2\.5\. Additional expansion cohort(s) of squamous oesophageal cancer if confirmed as recruiting by the Sponsor.
•2\.3\. At least one measurable lesion according to RECIST criteria Version 1\.1, that has had objective radiological progression on or after the last therapy.
•2\.4\. Consent for pre\-treatment and post\-treatment fresh tumour biopsy sample in a minimum of eight patients in the squamous NSCLC cohort, squamous oesophageal cohort (if confirmed as recruiting by the Sponsor) and all patients in the basket cohort (except patients with a very high MT1\-MMP H\-score if agreed with the Sponsor and PI as defined in the Laboratory Manual).

Exclusion Criteria

•1\. Radiotherapy (except for palliative reasons), systemic anti\-cancer therapy (except life\-long hormone suppression such as LHRH agents in prostate cancer) or investigational medicinal products during the previous four weeks (six weeks for nitrosoureas, mitomycin\-C) before treatment (or first dose of immunotherapy during the previous 12 weeks).
•2\. Prior bone marrow transplant, myeloablative conditioning, or extensive radiotherapy to greater than 25% of bone marrow, within the previous eight weeks of the first BT1718 dose.
•3\. Ongoing toxic manifestations of previous treatments greater than NCI CTCAE Grade 1\. Exceptions to this are alopecia, amenorrhea/oligospermia and any other ongoing toxic manifestation which in the opinion of the Investigator and the Medical Advisor should not exclude the patient.
•4\. Any CNS metastases (unless had local therapy and are asymptomatic and radiologically stable off steroids for the last four weeks).
•5\. Current or prior malignancy which could affect compliance with the protocol or interpretation of results. Patients with curatively\-treated non\-melanoma skin cancer, non\-muscle\-invasive bladder cancer, or carcinomas\-in\-situ are generally eligible.
•6\. Female patients who can become pregnant (or are already pregnant or lactating). However, those patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one effective form plus a barrier method) \[oral, injected or implanted hormonal contraception and condom; intra\-uterine device and condom; diaphragm with a spermicidal gel and condom] or agree to sexual abstinence, effective from the first administration of BT1718, throughout the trial and for six months afterwards are considered eligible.
•7\. Male patients with partners of child\-bearing potential (unless they agree to take measures not to father children by using a barrier method of contraception \[condom plus spermicide] or to sexual abstinence effective from the first administration of BT1718, throughout the trial and for six months afterwards. Men with partners of child\-bearing potential must also be willing to ensure that their partner uses an effective method of contraception for the same duration for example, hormonal contraception, intrauterine device, diaphragm with spermicidal gel or sexual abstinence). Men with pregnant or lactating partners must be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure of the foetus or neonate.
•8\. Surgery from which the patient has not yet recovered.
•9\. At high medical risk because of non\-malignant systemic disease including active uncontrolled infection.
•10\. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).