Clinical trial NCT05487170: A Study of RNK05047 in Subjects With Advanced Solid Tumors/Diffuse Large B-cell Lymphoma (CHAMP-1)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
DLBCL
Keywords: protein degrader
Lead sponsor: Ranok Therapuetics Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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
* Archived tumor tissue collected
* 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

Primary outcomes:
measure: Part 1: Incidence of DLTs
timeFrame: through 1 cycle/4 weeks
measure: Part 1: Incidence of TEAEs
timeFrame: through study completion, an average of 1 year
measure: Part 2: Incidence of TEAEs
timeFrame: through study completion, an average of 1 year
measure: Part 2: Objective response rate (ORR) based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
measure: Part 2: Duration of response (DoR) based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
measure: Part 2: Progression-free Survival (PFS) based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
measure: Part 2: Disease Control Rate (DCR) based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Part 1: Plasma concentration RNK05047
timeFrame: Through Cycle 3/approximately 12 weeks
measure: Part 1: ORR based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
measure: Part 1: DoR based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
measure: Part 1: PFS based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
measure: Part 1: DCR based on RECIST 1.1/RECIL 2017
timeFrame: through study completion, an average of 1 year
measure: Part 2: Plasma concentration RNK05047
timeFrame: Through Cycle 3/approximately 12 weeks
measure: Part 2: Overall Survival (OS)
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: New York
country: United States
facility: Weill Cornell - NY Presbyterian Hospital
state: New York
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Ranok Therapeutics
name: Linda Grummer
role: STUDY_DIRECTOR
References: