Clinical trial NCT05785728: A Study of DB-1202 Monotherapy in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Keywords: TGF-β
thyroid cancer
Lead sponsor: DualityBio Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-27
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0
timeFrame: up to 21 days after Cycle 1 Day 1
measure: Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Maximum Tolerated Dose (MTD) of DB-1202
timeFrame: 12 months
measure: Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1202
timeFrame: 12 months
measure: Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 2a: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.
timeFrame: Up to follow-up period, approximately 1 year post-treatment
Secondary outcomes:
measure: Phase 1 & Phase 2a: Pharmacokinetic-AUC
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: Pharmacokinetic-Cmax
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: Pharmacokinetic-Tmax
timeFrame: within 8 cycles (each cycle is 21 days)
measure: Phase 1 & Phase 2a: Pharmacokinetic-T1/2
timeFrame: within 8 cycles (each cycle is 21 days)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: DualityBio Inc.
name: Raymond Zhao
role: STUDY_DIRECTOR
References: