A Study of DB-1202 Monotherapy in Advanced Solid Tumors

Phase 1/2, Multicenter, Open-label, First-in-human Study of DB-1202 Monotherapy in Patients With Advanced Solid Malignant Tumors to Evaluate the Tolerability, Safety, Pharmacokinetics and Antitumor Activity

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1201 in subjects with advanced solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: DB-1202

Detailed Description

This is a multicenter, non-randomized, open-label, multiple-dose, FIH study. The study consists of two parts: Part 1 adopts a rule based "3 + 3" design to identify MTD/RP2D; Part 2 is a dose expansion phase to confirm the safety, tolerability and efficacy in selected solid malignant tumors.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jenny Y Li; Phone Number: 16502379339; Email: jenny.li@dualitybiologics.com
• Study Contact Backup: Name: Ren Y Yue; Email: ren.yue@dualitybiologics.com

Study Locations

• China
  • Shanghai, China, 200120
    • Fudan University Shanghai Cancer Center
    • Contact: Jian Zhang, PhD; Email: syner2000@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female at least 18 years old.
2. Has histologically or cytologically confirmed metastatic or locally advanced solid tumors for which no effective standard therapy existed or standard of care has failed or is not considered as an option.
3. Is capable of comprehending study procedures and risks outlined in the informed consent and is willing to provide written consent.
4. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
5. At least one measurable lesion as assessed by the investigator according to response evaluation criteria in solid tumors (RECIST) version 1.1 criteria.
6. Has adequate organ function within 7 days prior to initiation of the first Treatment Cycle
7. Platelet count ≥ 100 000/mm3
8. Hemoglobin (Hb) ≥ 8.5 g/dL
9. Absolute neutrophil count (ANC) ≥ 1500/mm3
10. Creatinine ≤ 1.5 × upper limit of normal (ULN), or
11. Creatinine clearance ≥ 60 mL/min (modification Cockcroft-Gault equation)

Exclusion Criteria:

1. Has a medical history of symptomatic chronic heart failure (CHF) (New York Heart Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment.
2. Has a medical history of myocardial infarction or unstable angina within 6 months before Day 1.
3. Has a QTc prolongation to > 470 millisecond (ms) based on a 12-lead electrocardiogram (ECG) in triplicate.
4. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with a history of autoimmune thyroid disease are not excluded. Subjects with vitiligo or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
5. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
6. History of primary immunodeficiency.
7. History of allogeneic organ transplant.
8. Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
9. Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
10. Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7 days prior to initiation of the first Treatment Cycle.
11. Male and female subjects who are unwilling to use adequate contraceptive methods (double barrier or intrauterine contraceptive) during the study and for at least 7 months after the last dose of study drug.

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

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DB-1202 Dose Level 1; Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 1 on Day 1 of each cycle Q3W	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Level 2; Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 2 on Day 1 of each cycle Q3W	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Level 3; Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 3 on Day 1 of each cycle Q3W	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Level 4; Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 4 on Day 1 of each cycle Q3W	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Level 5; Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 5 on Day 1 of each cycle Q3W	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Level 6; Enrolled Subjects will receive a single-dose of DB-1202 at Dose Level 6 on Day 1 of each cycle Q3W	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Expansion 1; Enrolled Subjects with locally advanced or metastatic primary thyroid cancers with pathology of epithelial tumors that originated from thyroid follicular cells will be enrolled regardless of PD-L1 expression will receive initial dose of DB-1202 Q3W under a 21-day Treatment Cycle with RP2D.	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Expansion 2; Enrolled Subjects in selected solid malignant tumors can be added will receive initial dose of DB-1202 Q3W under a 21-day Treatment Cycle with RP2D.	Drug: DB-1202; Administered I.V.
Experimental: DB-1202 Dose Expansion 3; Enrolled Subjects in selected solid malignant tumors can be added will receive initial dose of DB-1202 Q3W under a 21-day Treatment Cycle with RP2D.	Drug: DB-1202; Administered I.V.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.	Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.	Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Phase 2a: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.	Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0	Percentage of participants in Part 1 with DLTs	up to 21 days after Cycle 1 Day 1
Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0	Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0	Up to follow-up period, approximately 1 year post-treatment
Maximum Tolerated Dose (MTD) of DB-1202	MTD on the data collected during Part 1	12 months
Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1202	RP2D of DB-1202 based on the data collected during Part 1	12 months
Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.	The percentage of subjects who had a best response rating of CR and PR, for Part 2 only which was maintained ≥4 weeks	Up to follow-up period, approximately 1 year post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 & Phase 2a: Pharmacokinetic-T1/2	Terminal elimination half-life	within 8 cycles (each cycle is 21 days)
Phase 1 & Phase 2a: Pharmacokinetic-AUC	Area under the concentration-time curve from time 0 to infinity of DB-1202	within 8 cycles (each cycle is 21 days)
Phase 1 & Phase 2a: Pharmacokinetic-Cmax	Maximum observed plasma concentration (Cmax) of DB-1202	within 8 cycles (each cycle is 21 days)
Phase 1 & Phase 2a: Pharmacokinetic-Tmax	Time to Cmax of DB-1202	within 8 cycles (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: DualityBio Inc.
• Investigators: Study Director: Raymond Zhao, DualityBio Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 28, 2023
• Primary Completion (Anticipated): February 28, 2024
• Study Completion (Anticipated): February 28, 2024

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: thyroid cancer; TGF-β
• Other Study ID Numbers: DB-1202-O-1001

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