Clinical trial NCT06554795: First-in-human Study of DB-1419 for Advanced/Metastatic Solid Tumors
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-1419 in Participants with Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Lead sponsor: DualityBio Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-15
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 1/2a First-in-Human Study of DB-1419 in Advanced/Metastatic Solid Tumors

Detailed description: A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1419 in Participants with Advanced/Metastatic Solid Tumors

Eligibility criteria: Inclusion Criteria:

1. Adults aged ≥ 18 years at the time of voluntarily signing informed consent.
2. Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor that has relapsed or progressed on or after standard systemic treatments, or refused the standard treatment, or for which no standard treatment is available.
3. At least one measurable lesion as assessed by the Investigator according to RECIST v1.1 criteria (Only applicable to backfill participants in phase 1a and participants in phase 1b/2a). CRPC participants with bone-only disease may be eligible on a case-by-case basis after discussion with the Medical Monitor.
4. Has a life expectancy of ≥ 3 months.
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
6. Has LVEF ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
7. Has adequate organ function within 7 days prior to the first dose of study treatment.
8. Has adequate treatment washout period prior to the first dose of study treatment.
9. Is willing to provide pre-existing resected tumor samples when available or undergo fresh tumor biopsy if feasible for the measurement of B7-H3/PD-L1 level and other biomarkers if no contraindication.

   Note: there is no minimum B7-H3/PD-L1 expression level mandatory for entry into the study.
10. 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.

Exclusion Criteria:

1. Prior treatment with B7-H3 targeted therapy.
2. Has a medical history of symptomatic congestive heart failure (New York Heart Association \[NYHA\] classes II-IV or serious cardiac arrhythmia requiring treatment.
3. Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.
4. Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to \> 470 millisecond (ms) in males and females based on a 12-lead electrocardiogram (ECG) in triplicate.
5. Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis which needs glucocorticoids and antibiotics) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening.
6. Has a history of underlying pulmonary disorder including, but not limited to, pulmonary emboli within 3 months of the start of study treatment, severe asthma, severe COPD, restrictive lung disease, and other clinically significant pulmonary compromise or requirement for supplemental oxygen.
7. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
8. Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals within 2 weeks before first dose of study treatment.
9. Know human immunodeficiency virus (HIV) infection.
10. Has spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with asymptomatic CNS metastases who are radiologically and neurologically stable for at least 4 weeks following CNS-directed therapy (defined as 2 brain images, same imaging modality, both of which are obtained after treatment to the brain metastases; these imaging scans should be obtained at least 4 weeks apart and show no evidence of intracranial progression), and are on stable or decreasing doses of corticosteroids equivalent to ≤10 mg/day prednisone are eligible for study entry.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Phase 1/2a: Percentage of Participants with Adverse events (AE) serious AE (SAE)
timeFrame: Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first
measure: Phase 1/2a: Percentage of Participants with serious AE (SAE)
timeFrame: Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first
measure: Phase 1a: Maximum Tolerated Dose (MTD)
timeFrame: From first study treatment administration until the initiation of Phase1b/2a, approximately up to 12 months.
measure: Phase 1a: Recommended Phase 2 Dose (RP2D)
timeFrame: From first study treatment administration until the initiation of Phase 1b/2a, approximately up to 12 months.
measure: Phase 1b/2a: Objective Response Rate (ORR) determined by Investigator per RECIST v1.1
timeFrame: Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months.
Secondary outcomes:
measure: Phase 1a: ORR determined from tumor assessments by Investigator per RECIST v1.1
timeFrame: Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months.
measure: Phase 1/2a: Progression free survival (PFS) determined from tumor assessments by Investigator per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1
timeFrame: Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months
measure: Phase 1/2a: OS
timeFrame: From the start date of study drug to the date of death due to any cause, whichever occurs first, approximately up to 12 months after last patient first dose.
measure: Phase 1/2a: AUC0-last
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
measure: Phase 1/2a: AUC0-tau
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
measure: Phase 1/2a: AUCinf
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
measure: Phase 1/2a: Cmax
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
measure: Phase 1/2a: Tmax
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
measure: Phase 1/2a: Ctrough
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
measure: Phase 1/2a: ADA prevalence
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
measure: Phase 1/2a: ADA incidence
timeFrame: within 8 cycles (each cycle is 21 days or 14 days)
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Site USA08-0
state: California
city: Washington, D.C.
country: United States
facility: Site USA06-0
state: District of Columbia
city: Florida City
country: United States
facility: Site USA02
state: Florida
city: Edison
country: United States
facility: Site USA04-0
state: New Jersey
city: Carolina
country: United States
facility: Site USA03
state: North Carolina
city: Philadelphia
country: United States
facility: Site USA05-0
state: Pennsylvania
city: Nashville
country: United States
facility: Site USA07-0
state: Tennessee
city: North Ryde
country: Australia
facility: AUS03-0
state: New South Wales
city: Randwick
country: Australia
facility: AUS01-0
state: New South Wales
city: Nedlands
country: Australia
facility: AUS02-0
state: Western Australia
city: Ha'erbin
country: China
facility: Site CHN08-0
state: Heilongjiang
city: Luoyang
country: China
facility: Site CHN03-0
state: Henan
city: Shanghai
country: China
facility: Site CHN06-0
state: Shanghai
city: Changchun
country: China
facility: Site CHN13-0
city: Shanghai
country: China
facility: Site CHN01-0
city: Shanghai
country: China
facility: Site CHN05-0
city: Zhengzhou
country: China
facility: Site CHN09-0
Study officials:
affiliation: DualityBio Inc.
name: Lily Hu
role: STUDY_DIRECTOR
References: