Trial Title:
A Clinical Trial of KVA12123 Treatment Alone and in Combination With Pembrolizumab In Advanced Solid Tumors (VISTA-101)
NCT ID:
NCT05708950
Condition:
Cancer
Solid Tumor
Melanoma
Carcinoma
Sarcoma
Lung Cancer
Prostate Cancer
Breast Cancer
Colo-rectal Cancer
Uterine Cancer
Pancreatic Cancer
Gastric Cancer
Esophageal Cancer
Thyroid Cancer
Ovarian Cancer
Kidney Cancer
Head and Neck Cancer
Conditions: Official terms:
Kidney Neoplasms
Uterine Neoplasms
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
KVA12123 - Dose Escalation
Description:
Ascending KVA12123 doses given as monotherapy by intravenous administration every 2 weeks
of each 6-week cycle.
Arm group label:
KVA12123 Monotherapy Dose Escalation
Intervention type:
Drug
Intervention name:
KVA12123 Plus Pembrolizumab - Dose Escalation
Description:
Ascending KVA12123 doses given by intravenous administration every 2 weeks of each 6-week
cycle in combination with a fixed dose of pembrolizumab administered once every 6 week
cycle.
Arm group label:
KVA12123 Plus Pembrolizumab Dose Escalation
Other name:
Keytruda
Intervention type:
Drug
Intervention name:
KVA12123 - Dose Expansion
Description:
KVA12123 administered at the RP2D by intravenous administration every 2 weeks of each 6
week cycle.
Arm group label:
KVA12123 Monotherapy Dose Expansion
Intervention type:
Drug
Intervention name:
KVA12123 Plus Pembrolizumab - Dose Expansion
Description:
KVA12123 administered at the RP2D by intravenous administration every 2 weeks in
combination with a fixed dose of pembrolizumab administered once every 6 week cycle.
Arm group label:
KVA12123 Plus Pembrolizumab Dose Expansion
Other name:
Keytruda
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria
1. Willing and able to provide informed consent.
2. Be at least 18 years of age at the time of consent.
3. Has histologically or cytologically confirmed, locally advanced or metastatic solid
tumor that has progressed or was non-responsive to standard of care therapy and for
which no available curative therapy exists.
4. Has expected survival ≥16 weeks.
5. Presence of measurable disease by iRECIST.
6. Has an ECOG performance status score of 0 or 1.
7. Has adequate organ function within 10 days prior to the start of study treatment.
8. Has normal thyroid function or hypothyroid with stable supplementation.
9. Has consented to the collection of archival tissue prior to study treatment
initiation.
10. Participants with prior exposure to systemic anticancer therapy including
investigational agents following a 4-week washout period are eligible. Participants
with prior small molecule targeted therapy or other short half-life drugs are
eligible following a 2-week washout period.
11. Participants having prior curative radiation therapy completed 2 weeks prior to
study drug administration or prior palliative radiation therapy to non-CNS disease
completed at least 1 week prior to study drug administration are eligible.
12. HIV-infected participants must be on anti-retroviral therapy (ART) and have a
well-controlled HIV infection/disease.
13. Participants with a history of HBV infection having durable HBsAg loss and
undetectable serum HBV DNA no longer requiring treatment are eligible.
14. Participants with history of HCV infection are eligible if HCV viral load is
undetectable at screening and participants have completed curative antiviral
therapy.
15. Post-menopausal women and surgically sterile men and women are permitted.
16. Patients of childbearing potential are permitted to participate under the following
conditions:
1. Must have negative urine pregnancy test result within 72 hrs prior to the first
dose of any study drug
2. Must agree not to become pregnant during the study and for 120 days after the
final dose of any study drug
3. Must agree not to breastfeed or donate ova, starting at time of informed
consent and continuing through 120 days after the final dose of any study drug
4. If sexually active in a way that could lead to pregnancy, must consistently use
2 acceptable methods of birth control (contraception), at least 1 of which must
be highly effective starting at time of informed consent and continuing
throughout the study and for 120 days after the final dose of any study drug.
17. Patients who can father children are permitted to participate under the following
conditions:
1. Must agree not to donate sperm starting at the time of informed consent and
continuing throughout the study period and for 120 days after the final dose of
any study drug
2. If sexually active with a person of childbearing potential in a way that could
lead to pregnancy, must consistently use 2 acceptable methods of birth control
(contraception), at least 1 of which must be highly effective starting at the
time of informed consent and continuing throughout the study and for 120 days
after the final dose of any study drug
3. If sexually active with a person who is pregnant or breastfeeding, must
consistently use a condom starting at time of informed consent and continuing
throughout the study and for 120 days after the final dose of any study drug.
18. Must be willing and able to comply with the trial procedures and the follow-up
schedule.
Exclusion Criteria
1. Untreated CNS metastatic disease, leptomeningeal disease, or cord compression.
2. Concurrent cancer other than disease under study requiring systemic treatment.
Participants with basal cell or squamous cell skin cancer treated with curative
intent, carcinoma in-situ of the cervix or breast treated with curative intent, RAI
stage 0 Chronic Lymphocytic Leukemia, monoclonal gammopathy of undetermined
significance, superficial bladder cancer or very low and low risk prostate cancer
(localized Gleason score ≤ 6) under active surveillance are eligible.
3. Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years.
4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg QD of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study drug.
5. History of (non-infectious) pneumonitis/interstitial lung disease (ILD) that
required steroids or current pneumonitis/ILD.
6. Prior treatment with VISTA-targeted therapy.
7. Prior history of allogeneic, solid organ or stem cell transplant, or adoptive T-cell
transplant.
8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor
(e.g., CTLA-4, LAG-3, OX 40, CD137), and was discontinued from that treatment due to
a Grade 3 or higher immune-related adverse event (irAE).
9. Active known or suspected autoimmune disease that has required systemic treatment
within the past year. Replacement therapy (e.g., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.
10. Prior systemic anticancer therapy, including investigational agents, within 4 weeks
of treatment. Participants with prior small molecule targeted therapy or other short
half-life drugs are eligible following a 2-week washout period.
11. Has received prior radiation therapy within 2 weeks of start of study treatment or
has a history of radiation pneumonitis.
12. Has received radiation therapy to the lung that is >30 Gy within 6 months of the
first dose of study treatment.
13. Has received a live or live-attenuated vaccine within 30 days prior to the first
dose of study intervention.
14. Any requirement for daily supplemental oxygen.
15. Any condition requiring systemic treatment with corticosteroids (>10 mg QD
prednisone equivalents) or other immunosuppressive medications within 14 days before
the first dose of study drug.
16. Serious or poorly controlled cardiovascular disease.
17. Chronic hepatitis B or C.
18. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric
Castleman Disease.
19. Has an active infection requiring systemic therapy.
20. Known active or latent tuberculosis.
21. If the participant had major surgery, must have recovered adequately from the
procedure and/or any complications.
22. Toxicities arising from prior cancer therapy that have not resolved to Grade 1 or
baseline.
23. Red blood cell or platelet infusion within the preceding 2 weeks.
24. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study treatment.
25. Known hypersensitivity to any excipient contained in the drug formulation of
KVA12123.
26. Any significant history of drug allergy as assessed by the investigator.
27. Positive urine pregnancy test within 72 hrs of study drug administration.
28. Participants who are breastfeeding, pregnant, or planning to become pregnant from
time of informed consent until at least 120 days after final dose of study drug.
29. Has a history or current evidence of any condition, therapy, or laboratory
abnormality, or other circumstance that might confound the results of the study or
interfere with the participant's participation for the full duration of the study.
30. Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
31. Inability to comply with study procedures.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCLA Health (Santa Monica Cancer Care)
Address:
City:
Santa Monica
Zip:
90404
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christopher Lim
Phone:
310-829-5471
Email:
christopherlim@mednet.ucla.edu
Facility:
Name:
Sarah Cannon Research Institute at HealthONE
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sarah Kirk
Phone:
720-754-2610
Email:
CANN.DDUDenverGeneral@sarahcannon.com
Contact backup:
Last name:
Jason Henry, MD
Facility:
Name:
Sarah Cannon Research Institute at Florida Cancer Specialists
Address:
City:
Sarasota
Zip:
34232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Manish Patel, MD
Phone:
941-337-9993
Email:
mpatel@flcancer.com
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Contact:
Last name:
Paul Swiecicki, MD
Phone:
800-865-1125
Email:
CancerAnswerLine@med.umich.edu
Facility:
Name:
Thomas Jefferson University
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ida Micaily, MD
Email:
askPhase1@jefferson.edu
Facility:
Name:
Sarah Cannon Research Institute at Tennessee Oncology
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Benjamin Garmezy, MD
Start date:
March 3, 2023
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Kineta Inc.
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Kineta Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05708950
