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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; DLBCL
• Intervention / Treatment: Drug: RNK05047

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.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Linda Grummer, RN, BSN; Phone Number: 405-921-1605; Email: lindagrummer@ranoktherapeutics.com

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Winship Cancer Institute
      • Contact: Adam Burgess; Phone Number: 404-712-9858; Email: adam.burgess@emory.edu
      • Principal Investigator: Donald Harvey III, PharmD
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Recruiting
      • Horizon Oncology and Research Center
      • Contact: Kirsten Becker; Phone Number: 765-446-5111; Email: kbecker@verdioncology.com
      • Principal Investigator: Constantine Albany, MD
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell - NY Presbyterian Hospital
      • Principal Investigator: Manuel Hidalgo Medina, MD, PhD
      • Contact: Casey Owens, MPH; Email: cdo4001@med.cornell.edu
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Recruiting
      • Pennsylvania Cancer Specialists & Research Institute
      • Contact: Christine Nocera; Email: cnocera@pcsri.com
      • Principal Investigator: Satish Shah, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RNK05047; Dose-escalation of RNK05047 IV infusion	Drug: RNK05047; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Ranok Therapeutics (Hangzhou) Co., Ltd.
• Investigators: Study Director: Linda Grummer, Ranok Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: July 12, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: protein degrader
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: RNK05047-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No