Solid Tumor, AdultPhase 1HDAC6iNCT03008018
Safety,Tolerability and MTD KA2507 (HDAC6 Inhibitor) in Patients With Solid Tumours
A Phase 1 study testing KA2507 in people with Solid Tumor, Adult, run by Karus Therapeutics Limited at 1 site in United States.
Trial summary
The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult
- What is being tested?
- KA2507
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2017to 10 Jun 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years at the screening visit.
- Patients with histologically or cytologically documented, confirmed diagnosis of advanced malignancy, whose disease failed to respond to or progressed after standard therapy or they could not tolerate standard therapy.
- Measurable or evaluable disease according to RECIST v1.1.
- ECOG performance status of 0 or 1.
- Predicted life expectancy ≥12 weeks.
- For men and women of child-bearing potential, willing to use adequate contraception (i.e., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.
- 1. If female, must be either postmenopausal, sterilised or, if sexually active, effectively practicing an acceptable method of contraception (either oral, parenteral, or implantable hormonal contraceptives, intrauterine device or barrier and spermicide). Subjects must agree to use adequate contraception during the study and for at least 12 weeks (or longer as per local requirement) after the last dose of study treatment.
- 2. Male subjects agree to ensure that they or their female partner(s) use adequate contraception during the study and for at least 12 weeks (or longer as per local requirement) after the subject receives their last dose of study treatment.
Who cannot join
- Patients are not able to provide written informed consent to study participation
- Patients who have been treated with most recent radiotherapy, hormonal therapy, immunotherapy, chemotherapy or investigational drugs within ≤21 days or 5 half-lives (whichever is shorter) from enrolment (screening), and/or who have any unresolved NCI Common Terminology Criteria of Adverse Events (CTCAE) v4.03 > Grade 1 treatment-related side effect (with the exception of alopecia).
- Patient has anemia due to HbS or HbC disease, alpha or beta thalassaemia
- Patient has Glucose-6-phosphate deficiency
- Patient has known or suspected history of cytochrome b5-MetHb-reductase pathway deficiency
- Persons of Navajo, Athabaska Alaskan or Siberian Yakutsk descent
Show all 30Show fewer
- Patient has untreated severe hypothyroidism
- Patient has laboratory estimations indicating organ system dysfunction:
- Absolute neutrophil count (ANC) <1.5 X 109/L
- Platelets <100 X 109/L
- Hemoglobin <9g/dL
- Total bilirubin >1.5 mg/dL
- ALT and AST >3.0 times the ULN if no liver involvement or >5 times the ULN with liver involvement.
- Calculated creatinine clearance <60mL/min estimated using the Cockcroft-Gault equation:
- Cockcroft-Gault equation: creatinine clearance = (140 - age in years) x (wt in kg)) x 1.23) / (serum creatinine in micromol/l) [For women multiply the result of calculation by 0.85].
- Major surgery (excluding placement of vascular access) ≤21 days from beginning of the study drug or minor surgical procedures ≤7 days. No waiting is required following implantable port and catheter placement.
- Any of the following cardiac criteria:
- Congestive heart failure (CHF), grade III or IV per New York Heart Association (NYHA) classification
- Symptomatic cardiomyopathy
- > Class II Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Unstable angina or new-onset angina
- QTcF interval >470 ms on screening ECG.
- 9. Severe or uncontrolled systemic diseases including uncontrolled hypertension, active bleeding diatheses 10. Any evidence of active infection including active Hepatitis B, Hepatitis C or human immunodeficiency virus 11. The patient has concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease, uncontrolled hypertension, active bleeding diatheses).
- 12. Active infection requiring IV antibiotics within two weeks prior to treatment, or evidence of TB infection.
- 13. Hepatitis B, Hepatitis C or human immunodeficiency virus 14. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 3 weeks previously and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
- 15. Lactating, breastfeeding, or positive pregnancy test for female patients of child-bearing potential.
- 16. The patient is unable to swallow capsules and/or has a surgical or anatomical condition that precludes swallowing and absorbing oral medication on an ongoing basis (for oral therapy only).
- 17. Patients with prior stem cell transplantation or solid organ transplantation.
- 18. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years.
- 17. Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label Ascending Dose Study Evaluating the Safety/Tolerability, Pharmacokinetic and Pharmacodynamic Effects of KA2507 in Patients With Solid Tumours
The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study.
Following completion of the multiple ascending dose study, the protocol may be amended to include expansion cohorts in patients with melanoma and/or other solid tumors.
Read the detailed description
The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study.
Following completion of the multiple ascending dose study, the protocol may be amended to include expansion cohorts in patients with melanoma and/or other solid tumors.
This is a multiple ascending dosing (MAD) study of up to 6 treatment regimens cohorts based on using a 3+3 design (up to 36 patients overall). The principal objective is to establish the maximum tolerated dose, safety, tolerability and pharmacokinetic (PK) profile in blood and urine of this HDAC6 inhibitor in patients with solid tumors and to explore effects on pharmacodynamic markers of target engagement and response to treatment.
Daily/twice daily doses will be given as open label monotherapy. A review of safety and PK data will be conducted once the last patient in each cohort reaches day 28 of treatment. The review will confirm the dose to be used for the subsequent cohort. Dose escalation will be continued until the MTD is reached. Upon completion of the dose escalation phase of the study, dose expansion phases will be planned.
Patients responding to treatment may elect to remain on therapy until disease progression, death or the investigator decides to stop treatment.
- Conditions
- Solid Tumor, Adult
- Being tested
- KA2507
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KA2507Drug
Also called HDAC6 Inhibitor, HDAC6i
KA2507, an orally-active new chemical entity, is a potent and selective inhibitor of the HDAC6 enzyme, with potential clinical utility in the treatment of melanoma and other solid tumors. KA2507 has been shown to display potent in vitro activity in a range of cancer cell lines, including melanoma cell lines. KA2507 exerts potent in vivo efficacy in a syngeneic model of B16 melanoma. Here, the combination of the agent's direct tumor growth inhibition and metastasis suppression, coupled with its immunotherapeutic activity - demonstrated by decreased expression of STAT-3 and PD-L1 and increased expression of acetylated tubulin, gp100 and MHC Class I in tumors - have been observed.
| Study group | Role | What they receive |
|---|---|---|
| KA2507 (HDAC6 inhibitor) | Other | This is a single arm dose escalating study. Patients will be treated with open label KA2507 (HDAC6 inhibitor) capsules. Receives: Drug: KA2507 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The occurrence of dose limiting toxicity
- Any event with possible or probable relationship to study drug occurring up to day 28 from the start of treatment as assessed using the National Cancers Institutes Common Terminology Criteria for Adverse events version 4.03 therapy.
Measured: 28 days
Secondary outcomes (7)
Concentration of KA2507 in plasma over time (hours) post dosing
Measured: 24 weeks
Concentration of KA2507 in urine over time (hours) post dosing
Measured: 24 weeks
Blood concentration of histone acetylation during KA2507 treatment
Measured: 24 weeks
Blood concentration of tubulin during KA2507 treatment
Measured: 24 weeks
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Measured: 24 weeks
Clinical outcomes using the RECIST 1.1 criteria
Measured: 24 weeks
Clinical outcomes using Immuno-RECIST criteria
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2017 (estimated)
- Study start7 Aug 2017
- Primary completion10 Jun 2020
- Study completion10 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karus Therapeutics Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03008018
- Sponsor's protocol ID
- KTP-003
- Acronym
- HDAC6i
- Status last verified
- Aug 2020
- First submitted
- 21 Dec 2016
- Last updated
- 19 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tsimberidou AM, Beer PA, Cartwright CA, Haymaker C, Vo HH, Kiany S, Cecil ARL, Dow J, Haque K, Silva FA, Coe L, Berryman H, Bone EA, Nogueras-Gonzalez GM, Vining D, McElwaine-Johnn H, Wistuba II. Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors. Clin Cancer Res. 2021 Jul 1;27(13):3584-3594. doi: 10.1158/1078-0432.CCR-21-0238. Epub 2021 May 4.
PubMed 33947698
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Ascending Dose Study Evaluating the Safety/Tolerability, Pharmacokinetic and Pharmacodynamic Effects of KA2507 in Patients With Solid Tumours
- ClinicalTrials.gov ID
- NCT03008018
- Acronym / sponsor ID
- HDAC6i / KTP-003
- Conditions
- Solid Tumor, Adult
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Karus Therapeutics LimitedIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 10 Jun 2020 (actual)
- Study completion
- 10 Jun 2020 (actual)
- First posted
- 2 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study.
Following completion of the multiple ascending dose study, the protocol may be amended to include expansion cohorts in patients with melanoma and/or other solid tumors.
Detailed description
The aim of the study is to evaluate the safety/tolerability, pharmacokinetic, and pharmaco-dynamic effects of KA2507 and establish the maximum tolerated dose (MTD). Patients with PD-L1 expressing solid tumors which have relapsed or are refractory to prior treatment will be eligible to participate in this study.
Following completion of the multiple ascending dose study, the protocol may be amended to include expansion cohorts in patients with melanoma and/or other solid tumors.
This is a multiple ascending dosing (MAD) study of up to 6 treatment regimens cohorts based on using a 3+3 design (up to 36 patients overall). The principal objective is to establish the maximum tolerated dose, safety, tolerability and pharmacokinetic (PK) profile in blood and urine of this HDAC6 inhibitor in patients with solid tumors and to explore effects on pharmacodynamic markers of target engagement and response to treatment.
Daily/twice daily doses will be given as open label monotherapy. A review of safety and PK data will be conducted once the last patient in each cohort reaches day 28 of treatment. The review will confirm the dose to be used for the subsequent cohort. Dose escalation will be continued until the MTD is reached. Upon completion of the dose escalation phase of the study, dose expansion phases will be planned.
Patients responding to treatment may elect to remain on therapy until disease progression, death or the investigator decides to stop treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KA2507 (HDAC6 inhibitor) | Other | Drug: KA2507This is a single arm dose escalating study. Patients will be treated with open label KA2507 (HDAC6 inhibitor) capsules. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥18 years at the screening visit.
- Patients with histologically or cytologically documented, confirmed diagnosis of advanced malignancy, whose disease failed to respond to or progressed after standard therapy or they could not tolerate standard therapy.
- Measurable or evaluable disease according to RECIST v1.1.
- ECOG performance status of 0 or 1.
- Predicted life expectancy ≥12 weeks.
Key exclusion criteria (30 listed)
- Patients are not able to provide written informed consent to study participation
- Patients who have been treated with most recent radiotherapy, hormonal therapy, immunotherapy, chemotherapy or investigational drugs within ≤21 days or 5 half-lives (whichever is shorter) from enrolment (screening), and/or who have any unresolved NCI Common Terminology Criteria of Adverse Events (CTCAE) v4.03 > Grade 1 treatment-related side effect (with the exception of alopecia).
- Patient has anemia due to HbS or HbC disease, alpha or beta thalassaemia
- Patient has Glucose-6-phosphate deficiency
- Patient has known or suspected history of cytochrome b5-MetHb-reductase pathway deficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KA2507Also: HDAC6 Inhibitor, HDAC6iKA2507, an orally-active new chemical entity, is a potent and selective inhibitor of the HDAC6 enzyme, with potential clinical utility in the treatment of melanoma and other solid tumors. KA2507 has been shown to display potent in vitro activity in a range of cancer cell lines, including melanoma cell lines. KA2507 exerts potent in vivo efficacy in a syngeneic model of B16 melanoma. Here, the combination of the agent's direct tumor growth inhibition and metastasis suppression, coupled with its immunotherapeutic activity - demonstrated by decreased expression of STAT-3 and PD-L1 and increased expression of acetylated tubulin, gp100 and MHC Class I in tumors - have been observed. | Drug | KA2507 (HDAC6 inhibitor) |
Primary outcome
The occurrence of dose limiting toxicity
Time frame: 28 days
1. Any event with possible or probable relationship to study drug occurring up to day 28 from the start of treatment as assessed using the National Cancers Institutes Common Terminology Criteria for Adverse events version 4.03 therapy.
7 secondary outcomes
Concentration of KA2507 in plasma over time (hours) post dosing
Time frame: 24 weeks
Concentration of KA2507 in urine over time (hours) post dosing
Time frame: 24 weeks
Blood concentration of histone acetylation during KA2507 treatment
Time frame: 24 weeks
Blood concentration of tubulin during KA2507 treatment
Time frame: 24 weeks
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time frame: 24 weeks
Clinical outcomes using the RECIST 1.1 criteria
Time frame: 24 weeks
Clinical outcomes using Immuno-RECIST criteria
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2020.
- Derived from this study: PubMed 33947698Tsimberidou AM, Beer PA, Cartwright CA, Haymaker C, Vo HH, Kiany S, Cecil ARL, Dow J, Haque K, Silva FA, Coe L, Berryman H, Bone EA, Nogueras-Gonzalez GM, Vining D, McElwaine-Johnn H, Wistuba II. Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors. Clin Cancer Res. 2021 Jul 1;27(13):3584-3594. doi: 10.1158/1078-0432.CCR-21-0238. Epub 2021 May 4.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KA2507 in people with Solid Tumor, Adult, run by Karus Therapeutics Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The occurrence of dose limiting toxicity (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03008018, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2020.