A Phase 1 Cohort Dose Escalation and Expansion Trial to Determine the Safety, Tolerance, Maximum Tolerated Dose, and Preliminary Antineoplastic Activity of IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas (NHL)
Overview
- Phase
- Phase 1
- Intervention
- IKS03
- Conditions
- Not specified
- Sponsor
- Iksuda Therapeutics Limited
- Enrollment
- 80
- Locations
- 13
- Primary Endpoint
- Recommended Dose for Expansion (Part 1)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This first-in-human study will evaluate the recommended dose for further clinical development, safety, tolerability, antineoplastic activity, immunogenicity, pharmacokinetics and pharmacodynamics of IKS03, a CD19 targeting antibody-drug conjugate, in patients with advanced B cell non-Hodgkin lymphoma (NHL).
Detailed Description
The study will consist of 2 parts: dose-escalation (Part 1) and dose-expansion (Part 2). The dose-escalation part (Part 1) of the study is to evaluate the safety and tolerability of increasing dose levels of IKS03 to establish a recommended dose for expansion (RDE); and the dose-expansion part (Part 2) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of IKS03 at the RDE.
Investigators
David M. Browning
Scientific
Iksuda Therapeutics Limited
Eligibility Criteria
Inclusion Criteria
- •Males or females, ≥ 18 years of age
- •Part 1: documented B cell NHL (any subtype except Burkitt lymphoma, Waldenström macroglobulinemia, chronic lymphocytic leukemia); previously confirmed CD19-positive if feasible
- •Part 2: documented B cell NHL (subtypes to be determined); confirmed CD19-positive; possible expansion cohorts may include:
- •Diffuse large B cell lymphoma (including germinal center B cell type, activated B cell type)
- •Follicular lymphoma (including duodenal-type follicular lymphoma)
- •Mantle cell lymphoma
- •B cell lymphomas not specified
- •If B cell NHL subtype likely to have bone marrow involvement must be willing to undergo bone marrow biopsy in the event of an on-study complete response to confirm response
- •NHL that is relapsed, refractory to, or intolerant of existing therapy(ies) with known curative potential, or for which no standard therapy is available; must have received at least 2 prior lines of systemic therapy
- •Must be in need of systemic treatment and not require immediate cytoreductive therapy
Exclusion Criteria
- •Women who are pregnant or intending to become pregnant before, during, or within 8 months after the last dose of study drug; women who are breastfeeding
- •Patients documented to be CD19-negative
- •Central nervous system (CNS) lymphoma, leptomeningeal infiltration, or spinal cord compression not controlled by prior surgery or radiotherapy; symptoms suggesting CNS involvement
- •Part 2: History of another malignancy within 2 years, with the exception of:
- •Treated, non-melanoma skin cancers
- •Treated carcinoma in situ (e.g., breast, cervix)
- •Controlled, superficial carcinoma of the urinary bladder
- •T1a or b prostate carcinoma treated according to standard of care, with PSA within normal limits
- •Papillary thyroid carcinoma Stage I treated surgically for cure
- •Any of the following hematologic abnormalities at baseline (transfusion allowed \> 5 days previous):
Arms & Interventions
Dose Escalation Cohort (Part 1)
Each patient will receive repeat doses (by intravenous (IV) infusions) on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Intervention: IKS03
Dose Expansion: Diffuse-Large B-Cell Lymphoma Participants
Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Intervention: IKS03
Dose Expansion: Follicular Cell Lymphoma Participants
Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Intervention: IKS03
Dose Expansion: Mantle Cell Lymphoma Participants
Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Intervention: IKS03
Dose Expansion: Other B cell lymphoma (B-NHL not otherwise specified [NOS])
Each patient will receive IKS03 at the recommended dose for expansion (RDE) defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Intervention: IKS03
Outcomes
Primary Outcomes
Recommended Dose for Expansion (Part 1)
Time Frame: Up to 20 months
RDE will be determined using dose limiting toxicities (DLTs) and all other available study data
Objective Response Rate (Part 2)
Time Frame: up to 42 months
Antineoplastic effects will be assessed by Criteria for Response Assessment: The Lugano Classification (Cheson 2014)
Secondary Outcomes
- Evaluation of the immunogenicity of IKS03 (Part 1 and 2)(Up to 42 months)
- Plasma Concentrations of IKS03 (Part 1 and 2)(Up to 42 months)
- Determine recommended Phase 2 dose (RP2D) (Part 2)(Up to 42 months)