A Clinical Trial of KVA12123 Treatment Alone and in Combination With Pembrolizumab In Advanced Solid Tumors (VISTA-101)
- Conditions
- CancerSolid TumorKidney CancerMelanomaCarcinomaPancreatic CancerColo-rectal CancerGastric CancerEsophageal CancerOvarian Cancer
- Interventions
- Drug: KVA12123 - Dose ExpansionDrug: KVA12123 - Dose Escalation
- Registration Number
- NCT05708950
- Lead Sponsor
- Kineta Inc.
- Brief Summary
The goal of this clinical trial is to test the safety and efficacy of KVA12123 alone or combined with pembrolizumab in patients with advanced solid tumors. The main questions this study aims to answer are:
1. What is the safety of KVA12123 when administered alone and in combination with pembrolizumab to advanced cancer patients?
2. What is an appropriate dose of KVA12123 to administer alone and in combination with pembrolizumab to advanced cancer patients in future clinical trials?
Participants in this trial will be asked to:
1. Visit the clinical site every 1 - 2 weeks.
2. Receive KVA12123 every 2 weeks alone or in combination with pembrolizumab every 6 weeks.
3. Provide blood samples to evaluate drug levels in blood, drug safety and to explore the effects of each drug on the immune system.
4. Undergo scans every 6 weeks to test the effect of treatment on cancer progression.
5. Undergo other study procedures to evaluate drug safety and participant safety including physical exams, heart function tests, etc.
- Detailed Description
This is a first-in-human (FIH), Phase 1/2, open-label, multicenter, dose escalation, and dose expansion study designed to evaluate the safety, tolerability, PK, immunogenicity, and tumor response of the investigational drug KVA12123 alone and in combination with pembrolizumab in adults with relapsed or refractory advanced solid tumors. The study will be conducted in 4 parts: Parts A and B will focus on dose escalation (single-agent and in combination), and Parts C and D will focus on dose expansion (single-agent and in combination).
Parts A (single-agent KVA12123) and B (KVA12123 + pembrolizumab) will comprise up to 10 dose escalation cohorts (6 for Part A and 4 for Part B) and treat 1-6 participants in each cohort to characterize the safety, tolerability, pharmacodynamics (PD), pharmacokinetics (PK) and preliminary tumor responses of study interventions. The objective of Parts A and B will be to determine a recommended Phase 2 dose (RP2D) for Parts C and D.
Parts C (single-agent KVA12123) and D (KVA12123 + pembrolizumab) will comprise up to 7 disease-specific dose expansion cohorts (2 for Part C and 5 for Part D), which will commence at the RP2D to further characterize the safety, tolerability, PD, PK, and preliminary tumor response of KVA12123 alone and in combination with pembrolizumab.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 314
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description KVA12123 Plus Pembrolizumab Dose Escalation KVA12123 Plus Pembrolizumab - Dose Escalation Part B will consist of dose escalation with KVA12123 administered in combination with a fixed dose of pembrolizumab. KVA12123 Monotherapy Dose Expansion KVA12123 - Dose Expansion Part C will consist of dose expansion with KVA12123 administered as a single agent at the RP2D in participants with advanced solid tumors. KVA12123 Plus Pembrolizumab Dose Expansion KVA12123 Plus Pembrolizumab - Dose Expansion Part D will consist of dose expansion with KVA12123 administered at the RP2D in combination with a fixed dose of pembrolizumab. KVA12123 Monotherapy Dose Escalation KVA12123 - Dose Escalation Part A will consist of dose escalation with KVA12123 administered as a single agent in participants with advanced solid tumors.
- Primary Outcome Measures
Name Time Method Adverse Events Through study completion, an average of 1 year Type and frequency of adverse events as assessed by CTCAE v4.0.
AEs related to study drug Through study completion, an average of 1 year Type and frequency of treatment related adverse events as assessed by CTCAE v4.0.
Recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD) Through study completion, an average of 1 year Recommended Phase 2 dose (RP2D) or maximum tolerated dose (MTD) of KVA12123 when administered alone and in combination with pembrolizumab in participants with advanced solid tumors (milligrams or milligrams/kilogram).
- Secondary Outcome Measures
Name Time Method Pharmacokinetic (PK) profile of KVA12123 (Cmax) Through study completion, an average of 1 year maximum serum concentration (micrograms/milliliter \[mL\])
Pharmacokinetic (PK) profile of KVA12123 (Cmin) Through study completion, an average of 1 year trough serum concentration (micrograms/mL)
Pharmacokinetic (PK) profile of KVA12123 (tmax) Through study completion, an average of 1 year time to maximum serum concentration (hours)
Pharmacokinetic (PK) profile of KVA12123 (t1/2) Through study completion, an average of 1 year Elimination half life (hours)
Pharmacokinetic (PK) profile of KVA12123 (AUC) Through study completion, an average of 1 year Area under the concentration-time curve (microgram\*mL/hour)
Pharmacokinetic (PK) profile of KVA12123 (Vd) Through study completion, an average of 1 year Volume of distribution (milliliter or liter)
Pharmacokinetic (PK) profile of KVA12123 (Cl) Through study completion, an average of 1 year Clearance (mL/hour)
Concentration of anti-KVA12123 antibodies in serum Through study completion, an average of 1 year Change from baseline in anti-KVA12123 antibodies in serum (antibody concentration per mL)
Number of participants with progressive disease following treatment with KVA12123 Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Number of participants with progressive disease following treatment with KVA12123 in combination with pembrolizumab Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Number of participants with stable disease following treatment with KVA12123 Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Number of participants with stable disease following treatment with KVA12123 plus pembrolizumab Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Number of participants with partial response following treatment with KVA12123 Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Number of participants with partial response following treatment with KVA12123 plus pembrolizumab Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Number of participants with complete response following treatment with KVA12123 Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Number of participants with complete response following treatment with KVA12123 plus pembrolizumab Through study completion, an average of 1 year Investigator assessment of radiographic imaging according to iRECIST.
Trial Locations
- Locations (6)
Sarah Cannon Research Institute at Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute at HealthONE
🇺🇸Denver, Colorado, United States
UCLA Health (Santa Monica Cancer Care)
🇺🇸Santa Monica, California, United States
Sarah Cannon Research Institute at Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States