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This is a first-in-human, multicenter, open-label, single-arm, dose-escalation Phase 1 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity of D3L-002 monotherapy in subjects with advanced solid tumors. D3L-002 will be administered as an intravenous infusion every 3 weeks (Q3W) in 21-day cycles. Approximately 24 subjects will be enrolled. Dose escalation will follow a Bayesian Optimal Interval (BOIN) design to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| D3L-002 | Experimental | Dose Escalation
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| D3L-002 | Drug | D3L-002 is an investigational anti-TIGIT/anti-PVRIG bispecific antibody administered as an intravenous infusion every 3 weeks (Q3W). |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) | Incidence, nature, and severity of TEAEs and TRAEs assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 | From first dose through 30 days after the last dose (Safety Follow-up Visit) |
| Change from Baseline in Hemoglobin | Change from baseline in hemoglobin (g/dL) | From baseline through 30 days after the last dose |
| Change from Baseline in White Blood Cell Count | Change from baseline in white blood cell count (×10^9/L) | From baseline through 30 days after the last dose |
| Change from Baseline in Platelet Count | Change from baseline in platelet count (×10^9/L) | From baseline through 30 days after the last dose |
| Change from Baseline in Alanine Aminotransferase (ALT) | Change from baseline in alanine aminotransferase (ALT, U/L) | From baseline through 30 days after the last dose |
| Change from Baseline in Aspartate Aminotransferase (AST) | Change from baseline in aspartate aminotransferase (AST, U/L) | From baseline through 30 days after the last dose |
| Change from Baseline in Creatinine | Change from baseline in creatinine (mg/dL) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) | Maximum observed serum concentration of D3L-002 following intravenous administration | From Day 1 through End of Treatment (up to approximately 6 months) |
| Pharmacokinetics: Minimum (Trough) Concentration (Ctrough) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Contact | +86 21 61635900 | D3bio_CT@d3bio.com |
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| From baseline through 30 days after the last dose |
| Change from Baseline in Urine Protein | Change from baseline in urine protein (semi-quantitative or mg/dL per local laboratory standard) | From baseline through 30 days after the last dose |
| Change from Baseline in Urine Glucose | Change from baseline in urine glucose (semi-quantitative per local laboratory standard) | From baseline through 30 days after the last dose |
| Change from Baseline in Urine Blood | Change from baseline in urine blood (semi-quantitative per local laboratory standard) | From baseline through 30 days after the last dose |
| Change from Baseline in Systolic Blood Pressure | Change from baseline in systolic blood pressure (mmHg) | From baseline through 30 days after the last dose |
| Change from Baseline in Diastolic Blood Pressure | Change from baseline in diastolic blood pressure (mmHg) | From baseline through 30 days after the last dose |
| Change from Baseline in Heart Rate | Change from baseline in heart rate (beats per minute) | From baseline through 30 days after the last dose |
| Change from Baseline in Respiratory Rate | Change from baseline in respiratory rate (breaths per minute) | From baseline through 30 days after the last dose |
| Change from Baseline in Body Temperature | Change from baseline in body temperature (°C or °F). | From baseline through 30 days after the last dose |
| Change from Baseline in Physical Examination Findings | Evaluation of clinically significant changes from baseline in physical examination findings across body systems (e.g., cardiovascular, respiratory, neurological), as assessed by the investigator and categorized as normal or abnormal. | From baseline through 30 days after the last dose |
| Change from Baseline in Electrocardiogram (ECG) Parameters (QT Interval, PR Interval, QRS Duration, Heart Rate) | Evaluation of clinically significant changes from baseline in 12 lead electrocardiogram (ECG) parameters, including QT interval (milliseconds), PR interval (milliseconds), QRS duration (milliseconds), and heart rate (beats per minute). | From baseline through 30 days after the last dose |
| Determination of Maximum Tolerated Dose (MTD) | Determination of MTD based on dose-limiting toxicities (DLTs) occurring during the first cycle (21 days); MTD defined as the dose with estimated DLT rate closest to 30% using a BOIN design | Cycle 1 (Day 1 through Day 21) |
| Determination of Recommended Phase 2 Dose (RP2D) | Determination of RP2D based on the totality of safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary efficacy data | Through end of dose-escalation phase (approximately up to 3 months following last subject's first dose) |
Predose serum concentration of D3L-002 at steady state |
| From Day 1 through End of Treatment (up to approximately 6 months) |
| Pharmacokinetics: Time to Maximum Concentration (Tmax) | Time from dosing to maximum observed serum concentration of D3L-002 | From Day 1 through End of Treatment (up to approximately 6 months) |
| Pharmacokinetics: Terminal Half-Life (t½) | Terminal elimination half-life of D3L-002 calculated from serum concentration-time data | From Day 1 through End of Treatment (up to approximately 6 months) |
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) | Area under the serum concentration-time curve of D3L-002 | From Day 1 through End of Treatment (up to approximately 6 months) |
| Immunogenicity: Incidence of Anti-Drug Antibodies (ADA) | Incidence of subjects with detectable anti-drug antibodies to D3L-002 | From baseline through Safety Follow-up Visit (up to 30 days after last dose) |
| Objective Response Rate (ORR) | Proportion of subjects achieving confirmed complete response (CR) or partial response (PR) per RECIST version 1.1 as assessed by investigators | From first dose through disease progression or end of study (up to approximately 12 months) |
| Duration of Response (DOR) | Time from first documented objective response (CR or PR) to disease progression or death | From first documented response until disease progression or death (up to approximately 12 months) |
| Disease Control Rate (DCR) | Proportion of subjects achieving CR, PR, or stable disease (SD) lasting at least 6 weeks per RECIST v1.1 | From first dose through disease assessment period (up to approximately 6 months) |
| Progression-Free Survival (PFS) | Time from first dose of D3L-002 to disease progression per RECIST v1.1 or death from any cause | From first dose until disease progression or death (up to approximately 12 months) |