A Study of RNK05047 in Subjects With Advanced Solid Tumors/Diffuse Large B-cell Lymphoma (CHAMP-1)

Study Overview
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Brief Summary
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This is a first in human, Phase 1/2 open-label multi-center, dose escalation and expansion study to evaluate the safety, tolerability, PK, PD and efficacy of RNK05047 when administered an intravenous (IV) infusion to subjects with advanced solid tumors, including diffuse large B-cell lymphoma (DLBCL). This is a 2-part study (dose escalation, cohort expansion) with sequential enrollment.

Detailed Description
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In Part 1, enrolled subjects will receive IV RNK05047 once weekly for 3 consecutive weeks in a 4-week cycle (no treatment in the fourth week). The dose-escalation phase will follow a standard 3+3 design, with 3 subjects enrolled into the first dosing cohort to receive RNK05047 at the starting dose of 0.75 mg/kg. In Part 2, once RP2D has been established, additional subjects (3 to 5 cohorts of approximately 15 subjects per cohort) will be enrolled in the cohort-expansion phase of the study. Tumor types for these cohorts will be determined based on data from the dose-escalation phase of the study and emerging results from preclinical studies or other scientific data. These dose expansion cohorts in all groups may be done concurrently.

Official Title
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A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Chaperone-mediated Protein Degrader RNK05047 in Subjects With Advanced Solid Tumors (CHAMP-1)

Conditions
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Advanced Solid Tumor, DLBCL

Intervention / Treatment
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* Drug: RNK05047


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically documented locally advanced or metastatic solid tumor Refractory or intolerant to all available standard-of-care therapies for advanced disease Measurable disease Adequate tumor sample ECOG Performance Status of 0 or 1 BMI ≥ 18 kg/m2 Adequate liver, renal, hematologic, and coagulation parameters Negative serum pregnancy test (for women of childbearing potential) at Screening and a negative urine or serum pregnancy test on Day 1 prior to the first infusion Males and females of childbearing potential must agree to use a highly effective method of contraception during treatment and for at least 4 months after the last dose of study treatment. Must be able to understand and comply with the conditions of the protocol and must have read and understood the consent form and provided written informed consent. Exclusion Criteria: Concurrent anticancer therapy: Radiotherapy, chemotherapy, biological therapy, or other anticancer investigational agents NOTE: at least 5 half-lives must have been ensued for any prior systemic cancer therapy agent before subject received the study drug on Day 1 Unresolved toxicities from prior anticancer therapy, defined as not having resolved according to CTCAE version 5.0 Grade ≤ 1, excluding Grade 1 alopecia Presence or suspicion of active central nervous system (CNS) metastases and/or leptomeningeal carcinomatosis Peripheral neurotoxicity ≥ Grade 2 according to CTCAE v5.0 Known active infection with HIV, HTLV-1, hepatitis B or C Women who are pregnant or breastfeeding History of another malignancy unless the subject has been treated with curative intent for this malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RNK05047<br>Dose-escalation of RNK05047 IV infusion | Drug: RNK05047<br>* RNK05047 is a chaperone-mediated protein degrader administered as IV infusion once weekly for 3 consecutive weeks in a 4-week cycle (no treatment in the fourth week).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Incidence of DLTs |  | through 1 cycle/4 weeks | 
| Part 1: Incidence of TEAEs |  | through study completion, an average of 1 year | 
| Part 2: Incidence of TEAEs |  | through study completion, an average of 1 year | 
| Part 2: Objective response rate (ORR) based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 
| Part 2: Duration of response (DoR) based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 
| Part 2: Progression-free Survival (PFS) based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 
| Part 2: Disease Control Rate (DCR) based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Plasma concentration RNK05047 |  | Through Cycle 3/approximately 12 weeks | 
| Part 1: ORR based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 
| Part 1: DoR based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 
| Part 1: PFS based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 
| Part 1: DCR based on RECIST 1.1/RECIL 2017 |  | through study completion, an average of 1 year | 
| Part 2: Plasma concentration RNK05047 |  | Through Cycle 3/approximately 12 weeks | 
| Part 2: Overall Survival (OS) |  | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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protein degrader