Advanced/metastatic malignancies, and preferred indications: head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), esophageal cancer, gastric cancer, melanoma, renal cell cancer, pancreatic cancer, cervical cancer, and triple negative breast cancer (BC) MedDRA version: 21.0 Level: LLT Classification code 10015362 Term: Esophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: KY1044
Product Code: KY1044
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: KY1044
Current Sponsor code: KY1044
Concentration unit: mg/ml milligram(s)/mil
Sponsors
Kymab Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study must meet all of the following criteria: 1. Written informed consent must be obtained prior to any procedures 2. Age =18 years (=20 years in Taiwan) 3. Histologically documented advanced/metastatic malignancies 4. Phase 1 and Phase 2 patients with advanced/metastatic malignancies who have measurable disease (non-measurable disease is allowed only in Phase 1) as determined by RECIST 1.1 (refer to Appendix 2) will be eligible if, according to the NCCN guidelines, there are no available therapies known to confer a clinical benefit for their disease, or they have exhausted all such available options. Additionally, the following specific tumor indications will be enrolled: a. Phase 1 (including enrichment part): Patients with advanced/metastatic malignancies, and preferred indications as identified in Section 3.1 (NSCLC, HNSCC, HCC, melanoma, cervical, gastric/esophageal, gastric, renal, pancreatic, and triple negative BC) b. Phase 2 KY1044 single agent: Patients with advanced/metastatic malignancies in indications in which signs of anti tumor activity (CR, PR or durable SD with tumor shrinkage that does not qualify for PR) were seen during the dose escalation of KY1044 as single agent. c. Phase 2 KY1044 in combination with atezolizumab: Patients with advanced/metastatic malignancies in the below selected indications, and/or indications which have shown promising activity in Phase 1: • NSCLC (anti PD (L)1 therapy naïve and pre treated) • Gastric/Esophageal (anti PD (L)1 therapy naïve and pre treated) • HNSCC (anti PD (L)1 therapy naïve and pre treated) • Esophageal (anti PD (L)1 therapy naïve and pre treated) • Cervical (anti PD (L)1 therapy naïve and pre treated) Indications, in which signs of anti tumor activity has been observed in Phase 1 with KY1044 in combination with atezolizumab 5. Prior therapy with anti-PD-(L)1 inhibitors is allowed provided any toxicity attributed to prior anti-PD-(L)1-directed therapy did not lead to discontinuation of therapy 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 7. Life expectancy longer than 12 weeks 8. Must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution’s guidelines. Patient must be willing to undergo a new tumor biopsy at screening, and during therapy on the study 9. Females of child bearing potential must be using two highly effective contraceptive measures for the duration of study participation and for at least 5 months after discontinuing study treatment, or longer if the half-life of KY1044 is observed to exceed that of atezolizumab (see Section 5.8). Females must not be breast feeding and must have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: - Post-menopausal defined as aged =50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments - Women less than 50 years old would be considered postmenopausal if they have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution - Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation 10. For the duration of
Exclusion criteria
Exclusion criteria: Patients eligible for this study must not meet any of the following criteria: 1. Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy, or increasing doses of corticosteroids within the prior 2 weeks of first dose of study treatment. Patients with treated brain metastasis unless neurologically stable (for 4 weeks post-treatment and prior to study enrolment) and off of steroids for at least 2 weeks before the first dose of study treatment 2. History of severe hypersensitivity reactions to other mAbs and/or their excipients 3. Known presence of neutralizing anti-atezolizumab antibodies (for patients previously treated with atezolizumab) 4. Having out of range laboratory values (creatinine, bilirubin, ALT, AST, Absolute neutrophil count , Platelet count, Hemoglobin) 5. Impaired cardiac function or clinically significant cardiac disease, including any of the following: - Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment, uncontrolled hypertension or clinically significant arrhythmia - QTcF >470 msec on screening ECG or congenital long QT syndrome - Acute myocardial infarction or unstable angina pectoris 12 hours) is prohibited within 4 weeks of the first dose of study treatment and patients requiring anticoagulant treatment should switch to low molecular weight heparin or anti Xa inhibitors with a half life of =12 hours. 15. Use of life attenuated vaccines against infectious diseases within 4 weeks of the first dose of study treatment 16. Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, 4 weeks is indicated as washout period 17. Major surgery within 2 weeks of the first dose of study treatment 18. Anti-CTLA4, anti-PD-(L)1 treatment within 4 weeks of the first dose of study trea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1: To characterize the safety and tolerability of KY1044 as single agent and in combination with atezolizumab and to identify recommended doses for future studies. Phase 2: To estimate the anti-tumor efficacy of KY1044 as single agent and in combination with atezolizumab.;Secondary Objective: - To evaluate the preliminary anti-tumor activity of KY1044 as single agent and in combination with atezolizumab (Phase 1 only) - To characterize the safety and tolerability of KY1044 as single agent and in combination with atezolizumab (Phase 2 only) - To characterize the PK profile of KY1044 as single agent and in combination with atezolizumab - To assess emergence of anti-KY1044 and anti-atezolizumab antibodies following one or more i.v. infusions of KY1044 single agent and/or in combination with atezolizumab - To assess changes in biomarkers - To describe the survival rate at 12 and 24 months of patients treated with KY1044 as single agent and in combination with atezolizumab for each disease group;Primary end point(s): Phase 1 - Safety: Incidence and severity of AEs and SAEs, including changes in laboratory parameters, vital signs and electrocardiograms (ECGs) - Tolerability: Dose interruptions, reductions and dose intensity - The incidence of DLTs with KY1044 as single agent during the first 21 days of treatment - The incidence of DLTs with KY1044 in combination with atezolizumab during the first 21 days of treatment Phase 2 - ORR per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1);Timepoint(s) of evaluation of this end point: Phase 1 Safety evaluation and assessment of AEs throughout the study Phase 2 Tumor Imaging RECIST 1.1: at screening, every 8 weeks (±7 days) after the start of treatment for the first 16 weeks, after that every 12 weeks (±7 days) till the end of 24 months of treatment or until objective disease progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy measures: - Best Overall Response (BOR), PFS and Duration of Response (DOR) per RECIST 1.1; - ORR and PFS per immune-related (i)RECIST (Phase 1 and Phase 2) - ORR per RECIST 1.1 (Phase 1 only) - Survival rate at 12 and 24 months Safety: - Safety: Incidence and severity of AEs and SAEs, including changes in laboratory parameters, vital signs and ECGs (Phase 2) 2. Tolerability: Dose interruptions, reductions and dose intensity (Phase 2) PK measures; KY1044 PK measures (e.g., Cmax, half-life); Serum concentration vs. time profiles Anti-drug antibodies; Presence and/or concentration of anti-KY1044 and anti-atezolizumab antibodies Biomarkers;Timepoint(s) of evaluation of this end point: Efficacy measures: - Tumor Imaging RECIST 1.1: at screening, every 8 weeks after the start of treatment for the first 16 weeks, after that every 12 weeks till the end of 24 months of treatment or until objective disease progression Safety: - Safety evaluation and assessment of AEs throughout the study - Tolerability assessed throughout the study PK measures; PK samples will be taken pre- and post-dose during all cycles and unscheduled at any time, when clinically indicated Anti-drug antibodies; ADA samples are collected at every cycle at pre-dose on Day 1 and unscheduled at any time, when clinically indicated Biomarkers | — |
Countries
Italy, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical trials information Kymab
Kymab Ltd
Outcome results
None listed