Safety, PK/PD, and Clinical Activity of KT-413 in Adult Patients With Relapsed or Refractory B-cell NHL
Study Details
Study Description
Brief Summary
This Phase 1a/1b study will evaluate the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in patients with R/R NHL. The Phase 1a stage of the study will explore escalating doses of single-agent KT-413. The Phase 1b stage will be split into 2 expansion cohorts to further characterize the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in MYD88 mutant and MYD88 wild-type R/R DLBCL.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1a Dose Escalation
|
Drug: KT-413
KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.
|
| Experimental: Phase 1b Dose Expansion MYD88MT KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 mutant DLBCL. |
Drug: KT-413
KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.
|
| Experimental: Phase 1b Dose Expansion MYD88WT KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 wild type DLBCL. |
Drug: KT-413
KT-413 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined dose level.
|
Outcome Measures
Primary Outcome Measures
- To establish the Maximum Tolerated Dose (MTD) [Within first 3 weeks of treatment]
Phase 1a
- Number of Participants with protocol specified Dose Limiting Toxicities (DLTs) [Within first 3 weeks of treatment]
Phase 1a
- Dose recommended for future studies [Within first 3 weeks of treatment]
Phase 1a/1b
- Clinical Laboratory Abnormalities [Clinical laboratory abnormalities will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy]
Incidence and severity of clinical laboratory abnormalities in serum chemistry, hematology, coagulation parameters, and urinalysis tests as assessed by CTCAE v5.0 (Phase 1a/1b)
- Adverse Event Parameters [Adverse Event Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy]
Incidence and severity of adverse events as assessed by CTCAE v5.0 (Phase 1a/1b)
- ECG Parameters [ECG Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy]
Changes in the ECG parameters, including heart rate and measures PR, QRS, QT, and QTc intervals as assessed by CTCAE v5.0 Phase 1a/1b
Secondary Outcome Measures
- Area under the plasma concentration versus time curve for KT-413 from time zero to last quantifiable time point (AUC0-t) [Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)]
Phase 1a/1b
- Maximum Plasma Concentration of KT-413 (Cmax) [Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)]
Phase 1a/1b
- Time of maximum plasma concentration of KT-413 (Tmax) [Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)]
Phase 1a/1b
- Half-life of KT-413 [if data permits (T1/2)] [Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)]
Phase 1a/1b
- Amount of KT-413 excreted in urine from time zero to last collected timepoint (Ae0-t) [Urine samples for PK analysis collected during the first cycle (21 day cycle)]
Phase 1a/1b
- Evidence of clinical activity of KT-413 as determined by Objective Response Rate (ORR) [From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months]
Phase 1a/1b
- Duration of Response (DOR) as assessed by the Investigator [From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months]
Phase 1a/1b
- Progression-free survival (PFS) as assessed by the Investigator [From time of entry on study through progression, up to 18 months]
Phase 1b
- Disease Control Rate (DCR) as assessed by the investigator [From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months]
Phase 1b
- Overall Survival (OS) as assessed by the investigator [From time of entry on study through death or date last known alive at end of follow-up, up to 18 months]
Phase 1b
Other Outcome Measures
- KT-413 levels in peripheral blood mononuclear cells [Blood samples for PD analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days)]
Phase 1a/1b
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Phase 1a Only: Histologically confirmed diagnosis of B-cell NHL according to the 2016 World Health Organization (WHO) classification. Diffuse large B-cell lymphoma (DLBCL) includes: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; human herpesvirus 8 (HHV8) positive DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type. Patients with indolent lymphoma are eligible if they meet criteria for systemic treatment.
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Phase 1b Only: Histologically confirmed diagnosis of DLBCL according to the 2016 WHO classification including: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; HHV8+ DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type.
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Disease relapsed and/or refractory to at least 2 accepted standard systemic regimens.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening.
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Adequate organ and bone marrow function, in the absence of growth factors
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Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol
Exclusion Criteria:
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Known CNS lymphoma or meningeal involvement.
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History of or active concurrent malignancy other than B-cell NHL or DLBCL unless the patient has been disease-free for ≥ 2 years. Exceptions to the ≥ 2-year time limit include treated basal cell or localized squamous cell skin carcinoma, localized prostate cancer, or other localized carcinomas such as carcinoma in situ of cervix, breast, or bladder.
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Infection with hepatitis B (HBV), hepatitis C (HCV), or known history of or current active viral infection with human immunodeficiency virus (HIV).
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Radiation treatment within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
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Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
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Ongoing unstable cardiovascular function including history of myocardial infarction within 3 months of planned start of study drug.
-
Patient has not recovered from any clinically significant AEs of previous treatments to pre-treatment baseline or Grade 1 prior to first dose of study drug.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Norton Cancer Institute | Louisville | Kentucky | United States | 40207 |
| 2 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 3 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 4 | University of Virginia Comprehensive Cancer Center | Charlottesville | Virginia | United States | 22903 |
Sponsors and Collaborators
- Kymera Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KT413-DL-101