A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors

DualityBio

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: HER2-positive Advanced Solid Tumor

Treatments: Drug: Itraconazole; Biological: DB-1303/BNT323; Drug: Ritonavir; Drug: Pertuzumab Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT05150691

DB-1303-O-1001

Details and patient eligibility

About

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303/BNT323 in subjects with advanced solid tumors that express HER2.

Full description

This is a multicenter, non-randomized (Except for Dose Expansion 1 and Dose Expansion 9 cohorts), 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.

Enrollment: 796 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Additional Inclusion Criteria for Part 2 Expansion Group 9:

1. Has pathologically documented advanced/unresectable, recurrent, or metastatic EC (including UCS and USPC) and has progressed on or after at least 1 line of systemic treatment including platinum-based therapy and exposure to ICI but no more than prior 3 lines of therapy for advanced/unresectable, or metastatic disease. Note: endocrine therapy will not qualify as a systemic therapy line.

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.
• Part 2 (expansion) Only: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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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796 participants in 24 patient groups

DB-1303/BNT323 Dose Level 1

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 1 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Level 2

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 2 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Level 3

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 3 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Level 4

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 4 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Level 5

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 5 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 1

Experimental group

Description:

Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 2

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 3

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 4

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 5

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Level 6

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 6 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Level 7

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 7 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 6

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 7

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 8

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 9

Experimental group

Description:

Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 on Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 10

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W along with ritonavir or itraconazole to assess the DDI potential

Treatment:

Drug: Ritonavir

Biological: DB-1303/BNT323

Drug: Itraconazole

DB-1303/BNT323 Dose Expansion 11

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 12

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 in combination with Pertuzumab on Day 1 of each cycle Q3W

Treatment:

Drug: Pertuzumab Injection

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 13

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 14

Experimental group

Description:

China Only:Subjects who were previously treated with trastuzumab and taxane will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 15

Experimental group

Description:

China Only: Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 16

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323

DB-1303/BNT323 Dose Expansion 17

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Treatment:

Biological: DB-1303/BNT323