Advanced solid tumour types which are known to have a high frequency of TROP2 positivity (e.g., head and neck squamous cell carcinoma [HNSCC], urothelial, breast cancer, non-small cell lung cancer [NSCLC]) Cancer
Conditions
Interventions
In the monotherapy dose escalation (Module A), KJ-103 will be administered in escalating doses (multiple participant cohorts consisting of 3–6 participants). Participants will receive KJ-103 intraveno
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Age
16 Years to 100 Years
Inclusion criteria
Inclusion criteria: Core Inclusion Criteria: 1. Written (signed and dated) informed consent and capable of co-operating with investigational medicinal product (IMP) administration and follow-up. 2. Histologically and/or cytologically confirmed diagnosis of advanced (incurable locally recurrent or metastatic) solid tumour (please refer to the specific inclusion criteria for each of the Modules for further details on tumour types). 3. At least 1 measurable target lesion, according to RECIST V1.1. Lesions which have previously received definitive radiotherapy can only be considered target lesions if there has been radiological disease progression since the completion of prior radiotherapy. 4. Eastern Cooperative Oncology Group performance status of 0–1 5. Haematological and biochemical indices within the ranges shown below. These measurements should be performed to confirm the participant’s eligibility to take part in the trial. 5.1. Haemoglobin (Hb) =90 g/L. Hb must be independent of transfusional support within last 14 days prior to testing 5.2. Absolute neutrophil count (ANC) =1.5 × 10e9/L (ANC must be independent of growth factor support within last 14 days prior to testing) 5.3. Platelet count =100 × 10e9/L must be independent of transfusional support within last 14 days prior to testing 5.4. Total bilirubin =1.5 × upper limit of normal (ULN); if known Gilbert syndrome: total bilirubin =3 × ULN 5.5. Alanine aminotransferase and aspartate aminotransferase =5 × ULN 5.6. Calculated creatinine clearance (using the Cockcroft & Gault formula) =50 mL/min 6. Aged 16 years or over at the time consent is given. 7. Patient must be able and willing to provide the following fresh tumour biopsy samples: 7.1. Pre-treatment biopsy – mandatory from participants in all Modules unless a fresh biopsy is not feasible due to a significant clinical risk. In such cases the suitability of an archival biopsy must be agreed between the investigator and the sponsor prior to enrolment. Use of an archival biopsy will not be allowed in Module A ‘backfill’ participants. 7.2. On-treatment biopsy in cohorts where this is mandated (Module A 'backfill' participants and all participants in Module B). Inclusion Criteria Specific for Module A (KJ-103 monotherapy dose escalation): 1. Documented radiological disease progression during or after their most recent line of anti-cancer therapy; have received 1 or more prior lines of systemic SoC anti-cancer therapy in the advanced setting for their respective cancer indication and are suitable for entry into a clinical trial in the opinion of the investigator. 2. Histologic or cytologic documentation of disease*: 2.1. HNSCC 2.2. Breast cancer 2.3. NSCLC 2.4. Urothelial carcinoma *Other types can be considered Inclusion Criteria Specific for Module B (KJ-103 given alongside pembrolizumab): 1. No local or systemic prior anti-cancer therapy given in the recurrent/metastatic disease setting. Histologic or cytologic documentation of squamous cell cancer of the oral cavity, oropharynx, larynx or hypopharynx, which is recurrent/metastatic or locally advanced and not amenable to local treatment with curative intent. 2. PD-L1 status known (combined positive score =1). Inclusion Criteria Specific for Module C (KJ-103 monotherapy dose expansion): 1. Documented radiological disease progression during or after their most recent line of anti-cancer therapy; have been previously treated with at least 1 and no more than 2 lines of systemic SoC anti-cancer t
Exclusion criteria
Exclusion criteria: 1. Previous treatment with anti-cancer therapies within the following timeframes: 1.1. Cytotoxic chemotherapy, mAbs, and/or small molecule tyrosine kinase inhibitors within 2 weeks prior to C1D1, or 5 half-lives, whichever is shorter. 1.2. Any investigational cancer treatment within 4 weeks prior to Cycle 1 Day 1 (C1D1) or 5 half-lives, whichever is shorter. 1.3. Radiation therapy (except for palliative reasons), within 2 weeks prior to C1D1. 1.4. Endocrine therapy (except when given for conditions other than malignant disease; e.g., thyroid replacement for hypothyroidism, hydrocortisone for cortisol deficiency/panhypopituitarism) 1.5. Participants with prior TROP2-targeted therapy are allowed 2. Co-administration of anti-cancer therapies other than those specified in this trial (with the exception of lifelong hormone suppression such as luteinising hormone releasing hormone agonists/analogues in prostate cancer). 3. Ongoing toxic manifestations of previous treatments greater than CTCAE Grade 1 (other than alopecia of any grade or Grade 2 peripheral neuropathy). Exceptions to this are any clinical stable AEs, which in the opinion of the Investigator should not exclude the patient. 4. Stroke or transient ischemic attack within 6 months prior to Screening. 5. Any central nervous system (CNS) metastases (unless the participant had local therapy and is asymptomatic and radiologically stable for at least 4 weeks prior to the first dose of KJ-103 [or pembrolizumab] and has been off steroids for the last 7 days prior to the first dose of KJ-103 or pembrolizumab [except for =10 mg prednisolone daily (or steroid equivalent)]). * Note: For participants with a history of CNS involvement, or a clinical suspicion of CNS involvement, brain imaging should be performed during Screening. 6. Women who are pregnant or breastfeeding (or planning to breastfeed). 7. Women of childbearing potential. Those participants who are not already pregnant or breastfeeding (or planning to breastfeed) are eligible, provided they have a negative highly sensitive serum pregnancy test within 7 days before enrolment and agree to follow the trial’s contraceptive requirements. 8. Male participants with partners of childbearing potential. Those participants who agree to follow the trial’s contraceptive guidance are eligible. 9. Major surgical procedure within 4 weeks of C1D1 or plans to undergo a major surgical procedure during the course of the trial. *Note: Procedures that are considered to be minimally invasive (e.g., peripherally inserted central catheter lines and/or port placements or minor biopsy procedures) will be exceptions. 10. At high medical risk because of non-malignant systemic disease, including active uncontrolled infection (defined as symptoms, signs, or radiographic) of bacterial, viral, or fungal or unknown aetiology requiring systemic therapy within 14 days of C1D1. A minimum 7-day washout prior to C1D1 must be observed for any antibiotic use. Participants with clinical and/or laboratory evidence of persistent infection must be excluded. Patients with previous HCV exposure but no current infection are eligible to participate. 11. Known to be serologically positive for the following: 11.1. HIV 11.2. HBsAg 11.3. HBcAb. Participants with a positive HBcAb test followed by a negative hepatitis B virus DNA test at Screening may be enrolled. 11.4. Hepatitis C virus antibody test. Participants with a positive HCV antibody test followed by a negative HCV RNA t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Dose for expansion determined following review of all clinically relevant data, including but not limited to toxicity, efficacy, PK and pharmacodynamic (PD) data. Evaluation of this endpoint will occur when all clinically relevant data in Module A have been reviewed by the sponsor, chief investigator and principal investigators. 2. Nature and frequency of dose-limiting toxicities (DLTs). DLTs are defined and assessed according to specific criteria in the trial protocol. Evaluation of this endpoint will occur when sufficient participants in Module A have completed the DLT observation period (first 21 days of administration). 3. Frequency of adverse events (AEs) considered at least possibly related to KJ 103 and number of Grade 3, 4 and 5 AEs considered at least possibly related to KJ-103. AEs, including relatedness, seriousness and severity (graded according to NCI-CTCAE v5.0), will be assessed by the Investigator. AEs will be collected from the date of informed consent until 10 weeks after the last administration of KJ-103 (or at least 4 months after the last dose of pembrolizumab for participants in Module B) or until the participant starts another anti-cancer therapy in Modules A and B. 4. Progression-free survival (PFS): defined as the time from the first dose of the trial intervention to the first occurrence of disease progression, as determined by the Investigator using RECIST V1.1, or death from any cause during the trial, whichever occurs first. Participants who are alive with no recorded progression at the time of analysis will be censored at the date of the scan when they were last recorded with an evaluable measure that was not progression. This endpoint will be evaluated at the end of trial for participants in Module B. 5. Objective response rate (ORR): defined as the percentage of participants who achieve complete response (CR) or partial response (PR) according to RECIST V1.1. This endpoint will be evaluated at the end of trial for participants in M | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. ORR. This endpoint will be evaluated at the end of the trial for participants in Modules A and B. 2. Clinical benefit rate (CBR): defined as the percentage of participants who achieve CR, PR, or stable disease (SD) according to RECIST V1. This endpoint will be evaluated at the end of trial for participants in Modules A and C. 3. Duration of response (DoR): defined as the period from the date of initial CR or PR until the date of progressive disease or death from any cause, whichever occurs first. DoR will be evaluated in the subset of participants with measurable disease at baseline who have achieved an objective response according to RECIST V1.1. This endpoint will be evaluated at end of trial for participants in Modules A and C. 4. PK parameters for KJ-103, including Cmax and Cmin for all participants, and total exposure (AUC), clearance, volume of distribution, and terminal elimination half-life for participants in Module A. Additional PK parameters may be determined as appropriate. Samples for PK analysis will be taken at up to 23 timepoints for participants in Modules A, B and C. 5. Dose for expansion of KJ-103 given alongside SoC pembrolizumab, determined following review of all clinically relevant data, including but not limited to toxicity, efficacy, PK and PD data. Evaluation of this endpoint will occur when all clinically relevant data in the safety run-in of Module B have been reviewed by the sponsor, chief investigator and principal investigators, and at the end of Module B. 6. Nature and frequency of DLTs. DLTs are defined and assessed according to specific criteria in the trial protocol. Evaluation of this endpoint will occur when sufficient participants in the safety run-in of Module B have completed the DLT observation period (first 21 days of administration) and all relevant data have been collected, and at the end of Module B 7. Time to response (TTR): defined as the time from the first dose of any trial drug to the date of the first documented | — |
Countries
England, United Kingdom
Contacts
Public ContactRashida;David Teladia;Gear
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Outcome results
None listed