A Phase 1/2a Study of DB-1310 in Advanced/Metastatic Solid Tumors

NCT05785741 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: DB-1310-O-1001CTR20231736
• Study Type: interventional
• Target: 1,000
• Locations: 2 countries
• Sites: 24

Brief Summary

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1310 in subjects with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

HER3; NSCLC; CRPC; HNSCC; BC; non-small cell lung cancer; castration-resistant prostate cancer; head and neck squamous cell carcinoma; breast cancer; ESCC; BTC

Outcome Measures

Primary Outcomes (8)

• Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. Percentage of participants in Part 1 with DLTs

  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 TEAE in Part 1 graded according to NCI CTCAE v5.0

  Up to follow-up period, approximately 1 year post-treatment

• 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

• Maximum Tolerated Dose (MTD) of DB-1310

  MTD on the data collected during Part 1

  12 months

• Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1310

  RP2D of DB-1310 based on the data collected during Part 1

  12 months

• Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.

  Percentage of participants with TEAE 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 2a: 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 Outcomes (9)

• Phase 1 & Phase 2a: Pharmacokinetic-AUC

  within 8 cycles (each cycle is 21 days)

• Phase 1 & Phase 2a: Pharmacokinetic-Cmax

  within 8 cycles (each cycle is 21 days)

• Phase 1 & Phase 2a: Pharmacokinetic-Tmax

  within 8 cycles (each cycle is 21 days)

• Phase 1 & Phase 2a: Pharmacokinetic-T1/2

  within 8 cycles (each cycle is 21 days)

• Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1

  with 8 cycles (each cycle is 21 days)

Study Arms (25)

DB-1310 Dose Level 1

EXPERIMENTAL

Enrolled Subjects will receive a single-dose of DB-1310 at Dose Level 1 on Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Level 2

EXPERIMENTAL

Enrolled Subjects will receive a single-dose of DB-1310 at Dose Level 2 on Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Level 3

EXPERIMENTAL

Enrolled Subjects will receive a single-dose of DB-1310 at Dose Level 3 on Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Level 4

EXPERIMENTAL

Enrolled Subjects will receive a single-dose of DB-1310 at Dose Level 4 on Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Level 5

EXPERIMENTAL

Enrolled Subjects will receive a single-dose of DB-1310 at Dose Level 5 on Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Level 6

EXPERIMENTAL

Enrolled Subjects will receive a single-dose of DB-1310 at Dose Level 1 on Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Level 7

EXPERIMENTAL

Enrolled Subjects will receive a single-dose of DB-1310 at Dose Level 1 on Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Level 8

EXPERIMENTAL

Enrolled subjects with HER2 positive BC who will receive DB-1310 on a selected dose level in combination with Trastuzumab

Drug: DB-1310; Drug: Trastuzumab

DB-1310 Dose Level 9

EXPERIMENTAL

Enrolled subjects with HER2 positive BC who will receive DB-1310 on a selected dose level in combination with Trastuzumab

Drug: DB-1310; Drug: Trastuzumab

DB-1310 Dose Level 10

EXPERIMENTAL

Enrolled subjects with HER2 positive BC who will receive DB-1310 on a selected dose level in combination with Trastuzumab

Drug: DB-1310; Drug: Trastuzumab

DB-1310 Dose Level 11

EXPERIMENTAL

Enrolled subjects with NSCLC subjects with EGFR Ex19del or L858R, G719X, S768I, L861Q alone or in combination with other EGFRm who will receive DB-1310 on a selected dose level in combination with Osimertinib

Drug: DB-1310; Drug: Osimertinib

DB-1310 Dose Level 12

EXPERIMENTAL

Enrolled subjects with NSCLC subjects with EGFR Ex19del or L858R, G719X, S768I, L861Q alone or in combination with other EGFRm who will receive DB-1310 on a selected dose level in combination with Osimertinib

Drug: DB-1310; Drug: Osimertinib

DB-1310 Dose Level 13

EXPERIMENTAL

Enrolled subjects with NSCLC subjects with EGFR Ex19del or L858R, G719X, S768I, L861Q alone or in combination with other EGFRm who will receive DB-1310 on a selected dose level in combination with Osimertinib

Drug: DB-1310; Drug: Osimertinib

DB-1310 Dose Expansion 1

EXPERIMENTAL

Enrolled Subjects with advanced/unresectable, or metastatic adenocarcinoma NSCLC with EGFR activating mutation who have progressed on or after standard systemic treatments will receive a single-dose of DB-1310 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Expansion 2

EXPERIMENTAL

Enrolled Subjects with advanced/unresectable, or metastatic NSCLC without EGFR activating mutation who have progressed on or after standard systemic treatments will receive a single-dose of DB-1310 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Expansion 3

EXPERIMENTAL

Enrolled Subjects with advanced/unresectable, or metastatic CRPC who have progressed on or after standard systemic treatments will receive a single-dose of DB-1310 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Expansion 4

EXPERIMENTAL

Enrolled Subjects with advanced/unresectable, or metastatic HNSCC who have progressed on or after standard systemic treatments will receive a single-dose of DB-1310 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Expansion 5

EXPERIMENTAL

Enrolled Subjects with advanced/unresectable, or metastatic BC with HER2-positive (IHC3+, or IHC2+ and ISH+) who have progressed on or after HER2 targeted systemic treatments will receive a single-dose of DB-1310 on a selected dose level Day 1 of each cycle Q3W in combination with trastuzumab deruxtecan.

Drug: DB-1310; Drug: Trastuzumab

DB-1310 Dose Expansion 6

EXPERIMENTAL

Enrolled Subject with other advanced/unresectable, or metastatic solid tumors who have progressed on or after standard systemic treatment, or for which no standard systemic treatment is available will receive a single-dose of DB-1310 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Drug: DB-1310

DB-1310 Dose Expansion 7

EXPERIMENTAL

Enrolled subjects with advanced/unresectable, or metastatic non-squamous NSCLC with EGFR exon 19 deletion or L858R mutation who haven't received any treatment in locally advanced, or metastatic disease will receive a single-dose of DB-1310 on a selected dose level Day 1 of each cycle Q3W in combination with Osimertinib.

Drug: DB-1310; Drug: Osimertinib

DB-1310 Dose Expansion 8

EXPERIMENTAL

Enrolled subjects with NSCLC with EGFR who will receive DB-1310 on a selected dose level in combination with Osimertinib

Drug: DB-1310; Drug: Osimertinib

DB-1310 Dose Expansion 9

EXPERIMENTAL

Enrolled subjects with NSCLC with KRAS mutation who will receive DB-1310 on a selected dose level (RP2D)

Drug: DB-1310

DB-1310 Dose Expansion 10

EXPERIMENTAL

Enrolled subjects with ESCC who will receive DB-1310 on a selected dose level (RP2D)

Drug: DB-1310

DB-1310 Dose Expansion 11

EXPERIMENTAL

Enrolled subjects with BTC who will receive DB-1310 on a selected dose level (RP2D)

Drug: DB-1310

DB-1310 Dose Expansion 12

EXPERIMENTAL

Enrolled subjects with HR+/HER2- BC who will receive DB-1310 on a selected dose level in monotherapy or combination with capecitabine

Drug: DB-1310; Drug: capecitabine

Interventions

capecitabine DRUG

Oral

DB-1310 Dose Expansion 12

DB-1310 DRUG

Administered I.V.

DB-1310 Dose Expansion 1; DB-1310 Dose Expansion 10; DB-1310 Dose Expansion 11; DB-1310 Dose Expansion 12; DB-1310 Dose Expansion 2; DB-1310 Dose Expansion 3; DB-1310 Dose Expansion 4; DB-1310 Dose Expansion 5; DB-1310 Dose Expansion 6; DB-1310 Dose Expansion 7; DB-1310 Dose Expansion 8; DB-1310 Dose Expansion 9; DB-1310 Dose Level 1; DB-1310 Dose Level 10; DB-1310 Dose Level 11; DB-1310 Dose Level 12; DB-1310 Dose Level 13; DB-1310 Dose Level 2; DB-1310 Dose Level 3; DB-1310 Dose Level 4; DB-1310 Dose Level 5; DB-1310 Dose Level 6; DB-1310 Dose Level 7; DB-1310 Dose Level 8; DB-1310 Dose Level 9

Trastuzumab DRUG

Administered I.V.

DB-1310 Dose Expansion 5; DB-1310 Dose Level 10; DB-1310 Dose Level 8; DB-1310 Dose Level 9

Osimertinib DRUG

Oral

DB-1310 Dose Expansion 7; DB-1310 Dose Expansion 8; DB-1310 Dose Level 11; DB-1310 Dose Level 12; DB-1310 Dose Level 13

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adults (defined as ≥ 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consent).
• Have relapsed or progressed on or after standard systemic treatments, or intolerable with standard treatment, or for which no standard treatment is available. Documented radiological disease progression during/after most recent treatment regimen for advanced/unresectable, or metastatic disease.
• At least one measurable lesion as assessed by the investigator according to response evaluation criteria in solid tumors (RECIST) version 1.1 criteria.
• Has a life expectancy of ≥ 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Has LVEF ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
• Is willing to provide archived tumor tissue or undergo fresh tumor biopsy for the retrospective measurement of human epidermal growth factor receptor 3 (HER3) level and other biomarkers if no contraindication. For HER2 IHC 0 breast cancer subjects, it is highly recommended to collect additional tumor sample (Refer to Lab Manual).
• Is capable of comprehending study procedures and risks outlined in the informed consent and able to provide written consent and agree to comply with the requirements of the study and the schedule of assessments.
• Male and female subjects of reproductive/childbearing potential must agree to use adequate contraceptive methods (e.g., double barrier or intrauterine contraceptive) during the study and for at least 4 months and 7 months after the last dose of study drug, respectively.
• Females must be using highly effective contraceptive measures during the study and for at least 7 months after the last dosing of study drug, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged 50 years or more and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration.
• Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.

You may not qualify if:

• Prior treatment with HER3 targeted therapy.
• Prior treatment with antibody drug conjugate with topoisomerase I inhibitor (except topoisomerase I inhibitor HER2 ADC for backfilled subjects in Combo A of Phase 1 and subjects in Cohort 2e of Phase 2a, and not applicable for subjects enrolled for DLT observation in Phase 1).
• Has a medical history of symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment.
• Has a medical history of myocardial infarction or unstable angina or cerebrovascular accident including transient ischemic attack (TIA) within 6 months before first dose. Or has uncontrolled hypertension (defined as systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg).
• Has any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval \> 250 milliseconds (ms).
• Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to \> 470 millisecond (ms) based on a 12-lead electrocardiogram (ECG) in triplicate.
• Unable or unwilling to discontinue concomitant drugs that are known to prolong the QT interval.
• For Combo B of Phase 1 and Cohort 2g, 2k of Phase 2a, patients currently receiving (or unable to stop use prior to receiving the first dose of Osimertinib) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3-week prior) (refer to Section 6.9.1) are ineligible, and all patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
• Has a history of (non-infectious) ILD/pneumonitis and/or radiation pneumonitis that required glucocorticoids, or has current ILD/pneumonitis and/or radiation pneumonitis, or where suspected ILD/pneumonitis and/or radiation pneumonitis cannot be ruled out by imaging at screening.
• Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months prior to Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disorder, restrictive lung disease, significant pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), and/or prior pneumonectomy (complete).
• Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals.
• Know human immunodeficiency virus (HIV) infection. Subjects should be tested for HIV prior to enrollment if required by local regulations or by the IRB/ EC.
• Subjects have active viral (any etiology) hepatitis are excluded.
• Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by serum pregnancy tests performed within 7 days prior to Cycle 1 Day 1.
• Has clinically active central nervous system (CNS) metastases, defined as untreated, or symptomatic, or requiring therapy with glucocorticoids or anticonvulsants to control associated symptoms. However, subjects with asymptomatic CNS metastases who are radiologically and neurologically stable for at least 4 weeks following CNS-directed radiotherapy or surgery, and who are on stable or decreasing doses of glucocorticoids equivalent to ≤10 mg/day prednisone are eligible for study entry.

Sponsors & Collaborators

• DualityBio Inc.: lead

Study Sites (24)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

RECRUITING

Research Site 117

Coral Gables, Florida, 33146, United States

WITHDRAWN

D&H Cancer Research Center LLC

Margate, Florida, 33063, United States

WITHDRAWN

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, 32827, United States

RECRUITING

BRCR global

Plantation, Florida, 33322, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

BRCR Medical Center Inc.

Tamarac, Florida, 33321, United States

RECRUITING

Research Site 111

Atlanta, Georgia, 30322, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Research site 119

Florham Park, New Jersey, 07932, United States

ACTIVE NOT RECRUITING

Carl & Edyth Lindner Center for Research & Education at The Christ Hospital and The Christ Hospital Cancer Center

Cincinnati, Ohio, 45219, United States

RECRUITING

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450003, China

RECRUITING

Hunan cancer hospital

Changsha, Hunan, 410000, China

RECRUITING

Jiangsu Province hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Affiliated Hospital of Jiangnan University

Wuxi, Jiangsu, 214000, China

RECRUITING

The first hospital of Jilin University

Changchun, Jilin, 130021, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, 110010, China

RECRUITING

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610030, China

RECRUITING

Research Site 222

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms

Interventions

Trastuzumab; osimertinib; Capecitabine

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Lily Hu

  DualityBio Inc.

  STUDY DIRECTOR

Central Study Contacts

Tiana Zhao

CONTACT

1-626-433-3820; tiana.zhao@dualitybiologics.com

Lingling Gu

CONTACT

lingling.gu@dualitybiologics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: March 27, 2023
• Study Start: August 17, 2023
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9); US (15)