A Study of DB-1303 in Advanced/Metastatic Solid Tumors
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| ClinicalTrials.gov Identifier: NCT05150691 |
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Recruitment Status :
Recruiting
First Posted : December 9, 2021
Last Update Posted : October 19, 2023
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Sponsor:
DualityBio Inc.
Information provided by (Responsible Party):
DualityBio Inc.
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Brief Summary:
This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303 in subjects with advanced solid tumors that express HER2.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HER2-positive Advanced Solid Tumor | Biological: DB-1303 Drug: Pertuzumab Injection Drug: Ritonavir Drug: Itraconazole | Phase 1 Phase 2 |
This is a multicenter, non-randomized, open-label, multiple-dose, FIH study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the MTD/RP2D; Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic HER2-expressing malignant solid tumors.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 631 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1303 in Patients With Advanced/Metastatic Solid Tumors |
| Actual Study Start Date : | January 31, 2022 |
| Estimated Primary Completion Date : | June 2025 |
| Estimated Study Completion Date : | October 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
|
Experimental: DB-1303 Dose Level 1
Enrolled Subjects will receive a single-dose of DB-1303 at Dose Level 1 on Day 1 of each cycle Q3W
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Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Level 2
Enrolled Subjects will receive a single-dose of DB-1303 at Dose Level 2 on Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Level 3
Enrolled Subjects will receive a single-dose of DB-1303 at Dose Level 3 on Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Level 4
Enrolled Subjects will receive a single-dose of DB-1303 at Dose Level 4 on Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Level 5
Enrolled Subjects will receive a single-dose of DB-1303 at Dose Level 5 on Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 1
Enrolled Subjects will be randomized to receive a single-dose of DB-1303 on a selected dose level 1 or dose level 2 Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 2
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 3
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 4
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 5
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Level 6
Enrolled Subjects will receive a single-dose of DB-1303 at Dose Level 6 on Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Level 7
Enrolled Subjects will receive a single-dose of DB-1303 at Dose Level 7 on Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 6
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 7
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 8
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 9
Enrolled Subjects will be randomized to receive a single-dose of DB-1303 on a selected dose level 1 or dose level 2 on Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 10
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W along with ritonavir and itraconazole to assess the DDI potential
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Biological: DB-1303
Administered IV Drug: Ritonavir Administered oral Drug: Itraconazole Administered oral |
|
Experimental: DB-1303 Dose Expansion 11
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
|
Experimental: DB-1303 Dose Expansion 12
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level 1 or dose level 2 in combination with Pertuzumab on Day 1 of each cycle Q3W
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Biological: DB-1303
Administered IV Drug: Pertuzumab Injection Administered IV |
|
Experimental: DB-1303 Dose Expansion 13
Enrolled Subjects will receive a single-dose of DB-1303 on a selected dose level (RP2D) Day 1 of each cycle Q3W
|
Biological: DB-1303
Administered IV |
Primary Outcome Measures :
- Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. [ Time Frame: up to 21 days after C1D1 ]Percentage of participants in Part 1 with DLTs
- Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) ot Treatment Emergent Adverse Event of Special Interest include those >/= G3 or leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0. [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0
- Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0
- Phase 1: Maximum Tolerated Dose (MTD) of DB-1303 [ Time Frame: 12 months ]MTD on the data collected during Part 1
- Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303 [ Time Frame: 12 months ]RP2D of DB-1303 based on the data collected during Part 1
- Phase 2: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) ot Treatment Emergent Adverse Event of Special Interest include those >/= G3 or leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0 [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0
- Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0
- Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1. [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]The percentage of subjects who had a best response rating of CR and PR, for Part 2 only which was maintained ≥4 weeks.
Secondary Outcome Measures :
- Phase 1 & Phase 2: Pharmacokinetic-AUC [ Time Frame: Pre-Dose, 30 minutes post end of infusion, 4 hours, 8 hours, 24 hours, 72 hours, 7 days, 14 days post start of infusion at Cycle 1 and Cycle 3. Pre-dose and within 30 minutes post end of infusion up to Cycle 8, End of Treatment and Safety Follow-up Visit ]Area under the concentration-time curve from time 0 to infinity of DB-1303
- Phase 1 & Phase 2: Pharmacokinetic-Cmax [ Time Frame: Pre-Dose, 30 minutes post end of infusion, 4 hours, 8 hours, 24 hours, 72 hours, 7 days, 14 days post start of infusion at Cycle 1 and Cycle 3. Pre-dose and within 30 minutes post end of infusion up to Cycle 8, End of Treatment and Safety Follow-up Visit ]Maximum observed plasma concentration (Cmax) of DB-1303
- Phase 1 & Phase 2: Pharmacokinetic-Tmax [ Time Frame: Pre-Dose, 30 minutes post end of infusion, 4 hours, 8 hours, 24 hours, 72 hours, 7 days, 14 days post start of infusion at Cycle 1 and Cycle 3. Pre-dose and within 30 minutes post end of infusion up to Cycle 8, End of Treatment and Safety Follow-up Visit ]Time to Cmax of DB-1303
- Phase 1 & Phase 2: Pharmacokinetic-T1/2 [ Time Frame: Pre-Dose, 30 minutes post end of infusion, 4 hours, 8 hours, 24 hours, 72 hours, 7 days, 14 days post start of infusion at Cycle 1 and Cycle 3. Pre-dose and within 30 minutes post end of infusion up to Cycle 8, End of Treatment and Safety Follow-up Visit ]Terminal elimination half-life
- Phase 1 & Phase 2: Pharmacokinetic-Ctrough [ Time Frame: Pre-Dose, 30 minutes post end of infusion, 4 hours, 8 hours, 24 hours, 72 hours, 7 days, 14 days post start of infusion at Cycle 1 and Cycle 3. Pre-dose and within 30 minutes post end of infusion up to Cycle 8, End of Treatment and Safety Follow-up Visit ]Trough concentration of DB-1303
- Phase 1 & Phase 2: Pharmacodynamics-ADA [ Time Frame: Before infusion on C1D1, C1D15, Before infusion on day 1 of C2, C4, C6, C8, C10 and every 4 cycles until end of treatment, EOT visit, Safety FU Visit, and 60 and 90 days after last dose (if possible) ]Data gathered from blood to determine Levels of anti-drug antibody (ADA) against DB 1303 in serum compared to baseline.
- Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1 [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]Proportion of participants who had a best response rating of CR or PR, or SD using RECIST V1.1.
- Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1 [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]The duration of time from date of first CR or PR to date of progressive disease or death due to any cause, whichever comes first using RECIST V1.1
- Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1 [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]The duration of time when receiving the first dose of study drug to the first date that is evaluated as either CR or PR using RECIST V1.1
- Phase 2: Time on Therapy [ Time Frame: Up to 21 days after the participant's last dose ]The duration of time from participant receiving first dose of study drug to the last dose + 21 days
- Phase 2: Percent change in target lesions as assessed by RECIST 1.1 [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]The percent change in the participant's target lesions from baseline to last study scan using RECIST V1.1
- Phase 2 Cohort b only: Progression-Free Survival [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]Time from subject receiving the first dose to disease progression or death by any cause
- Phase 2 Cohort b only: Overall Survival [ Time Frame: Up to follow-up period, approximately 1 year post-treatment ]Time from subject receiving the first dose to death by any cause
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Has a pathologically documented HER2-positive or HER2-expressing (except for cohort 2h where the requirement is HER2-null), advanced/unresectable, recurrent, or metastatic malignant solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- At least 1 measurable lesion (per RECIST 1.1)
- Provide signed informed consent
- ECOG performance status (PS) of 0-1.
- LVEF ≥ 50% by ECHO or MUGA
- Adequate organ functions
- Provide pre-existing diagnosis of HER2 status or resected tumor samples or undergo fresh tumor biopsy for HER2 testing.
- Life expectancy of ≥ 3 months.
Exclusion Criteria:
- History of symptomatic CHF (New York Heart Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment.
- History of myocardial infarction or unstable angina within 6 months before Day 1.
- Average QTcF > 450 ms in males and > 470 ms in females
- History of clinically significant lung diseases
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- HIV infection with AIDS defining illness or active viral hepatitis.
- Clinically active brain metastases
- Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline.
- A known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
- Multiple primary malignancies within 3 years, except adequately resected non- melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05150691
Contacts
| Contact: Britney Winterberger | +1-513-403-8568 | britney.winterberger@tigermedgrp.com |
Locations
Show 52 study locations
Sponsors and Collaborators
DualityBio Inc.
| Responsible Party: | DualityBio Inc. |
| ClinicalTrials.gov Identifier: | NCT05150691 |
| Other Study ID Numbers: |
DB-1303-O-1001 |
| First Posted: | December 9, 2021 Key Record Dates |
| Last Update Posted: | October 19, 2023 |
| Last Verified: | October 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by DualityBio Inc.:
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HER2 HER2-positive HER2-positive Breast Cancer HER2-positive Gastric Cancer HER2-positive Endometrial Cancer HER2-positive Biliary Tract Cancer HER2-positive Advanced Solid Tumor HER2 low HER2 high metastatic cancer HER2-positive GEJ Uterine serous papillary carcinoma USPC recurrent cancer carcinoma |
neoplasms breast neoplasms gastrointestinal neoplasms endometrial neoplasms biliary tract neoplasms Antineoplastic Agents, Biological stomach cancer bile duct cancer Cholangiocarcinoma liver cancer liver neoplasms NSCLC Non-Small Cell Lung Cancer NSCLC HER2 mutation HER2 Low Breast Cancer |
Additional relevant MeSH terms:
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Neoplasms Ritonavir Itraconazole Pertuzumab HIV Protease Inhibitors Viral Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents |
Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Antifungal Agents 14-alpha Demethylase Inhibitors Steroid Synthesis Inhibitors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Immunological Antineoplastic Agents |