Clinical Trial to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of DA-4505 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Locally Advanced or Metastatic Solid Tumors

an Open-Label, Phase 1/2a, First-in-Human Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of DA-4505 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Locally Advanced or Metastatic Solid Tumors

This study is an Open-Label, Phase 1/2a, First-in-Human, Dose-Escalation, Dose-Expansion, and Proof-of-Concept Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of DA-4505 as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Locally Advanced or Metastatic Solid Tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: DA-4505; Drug: DA-4505 + Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 and older.
2. Capable of giving signed informed consent.
3. Diagnosed with particular disease characteristics.
4. Expected survival ≥ 3 months.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. A female patient is eligible to participate if she is not pregnant or breastfeeding.
7. A male patient is eligible to participate if he agrees to remain abstinent or use a male condom when having sexual intercourse with a WOCBP, or if he has had a bilateral vasectomy.
8. Have measurable disease by revised RECIST v1.1 criteria.

Exclusion Criteria:

1. Inability to take oral medications or gastrointestinal abnormalities potentially impacting absorption.
2. Current enrollment or past participation in another clinical trial.
3. Unresolved adverse reactions (except alopecia) from previous cancer-directed therapy.
4. Use of cancer-directed therapies, including chimeric antigen receptor T cell therapy.
5. Autologous transplantation within 60 days.
6. Prior allogeneic transplantation.
7. Major surgery within 30 days, or unresolved complications after a major or minor surgery.
8. History of or currently active cardiovascular disease.
9. Clinically significant respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders.
10. History of other malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy; Phase 1a: Dose escalation Phase 1b: Dose expansion Phase 2a: Pharmacodynamic Biomarkers	Drug: DA-4505; Phase 1a: Dose escalation Phase 1b: OBD and MTD Phase 2a: RP2D
Experimental: Combination with Pembrolizumab; Phase 1a: Dose escalation Phase 1b: Dose expansion Phase 2a: Proof of concept Phase 2a: Pharmacodynamic Biomarkers	Drug: DA-4505 + Pembrolizumab; Phase 1a/b: OBD, MTD of DA-4505 + 200mg of Pembrolizumab Phase 2a: RP2D of DA-4505 + 200mg of Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of adverse events (AEs) meeting protocol-defined dose-limiting toxicity(DLT) criteria	The recommended Phase 2 dose(RP2D) will be the optimal biological dose (OBD) based on consideration of safety and tolerability information along with all available pharmacokinetic (PK), pharmacodynamic (PD), and efficacy data.	Cycle 1(21 days) in dose escalation
PK parameters for DA-4505 (Peak Plasma Concentration (Cmax))	Determine DA-4505 Cmax	Day 1 and 2 of first 2 cycles (every 21 days)
PK parameters for DA-4505 (Area Under the Curve (AUC))	Determine DA-4505 AUC	Day 1 and 2 of first 2 cycles (every 21 days)
PK parameters for DA-4505 (half-life (t1/2))	Determine DA-4505 half-life (t1/2).	Day 1 and 2 of first 2 cycles (every 21 days)
Response per revised "Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1)	To determine the anti-tumor activity of both DA-4505 as a single agent and in combination with pembrolizumab	approximately 12 months

Collaborators and Investigators

• Sponsor: Dong-A ST Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: February 15, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: DA4505_AMST_I/IIa

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No