Phase Ia/Ib Study of FXB0871 Monotherapy in Locally Advanced/Metastatic Solid Tumors

Phase 1Not Yet RecruitingNCT07558200

Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.138 enrolled

Overview

This is a phase 1a/1b, open-label, multicenter, dose-escalation and dose-expansion study evaluating the safety, tolerability, antitumor activity, pharmacokinetics, and pharmacodynamics of FXB0871 monotherapy in adults with selected locally advanced or metastatic solid tumors. In Part Ia, participants with selected solid tumors that have progressed after, are intolerant to, or are not suitable for standard therapy will receive FXB0871 in dose-escalation cohorts to determine the maximum tolerated dose and/or recommended phase 2 dose. In Part Ib, participants with PD-(L)1-resistant non-small cell lung cancer or hepatocellular carcinoma will receive FXB0871 in dose-expansion cohorts to further evaluate antitumor activity, safety, and dose optimization.

This first-in-human study consists of a dose-escalation part (Part Ia) and a dose-expansion part (Part Ib). In Part Ia, adults with selected locally advanced or metastatic solid tumors will receive FXB0871 monotherapy by intravenous infusion every 2 weeks in sequential pre-determinde dose cohorts using a Bayesian optimal interval design. The planned dosing schedule is every 2 weeks, with a dose-limiting toxicity observation period of the first 2 treatment cycles. Additional intermediate dose levels, cohort expansion, and schedule optimization to every 3 or 4 weeks may be allowed according to protocol-defined safety, PK/PD, and preliminary antitumor activity data. Part Ib will start after determination of the monotherapy recommended phase 2 dose (RP2D). Cohort A will enroll participants with PD-(L)1-resistant locally advanced or metastatic non-small cell lung cancer and randomize them 1:1 to receive FXB0871 at the RP2D or at a lower dose selected on the basis of Part Ia data. Cohort B will enroll participants with PD-(L)1-resistant locally advanced or metastatic hepatocellular carcinoma to receive FXB0871 at the RP2D. Participants may continue study treatment for up to 12 months or until unacceptable toxicity, disease progression, or another protocol-defined discontinuation criterion is met.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Interventions

Intervention1：FXB0871BIOLOGICAL

FXB0871 is administered by intravenous infusion at pre-determined dose level in Part Ia every 2 weeks. Treatment may continue for up to 12 months or until unacceptable toxicity, disease progression, or another protocol-defined discontinuation criterion is met.

Intervention2：FXB0871BIOLOGICAL

FXB0871 is administered by intravenous infusion at pre-determined dose level in Phase Ib every 2 weeks. Treatment may continue for up to 12 months or until unacceptable toxicity, disease progression, or another protocol-defined discontinuation criterion is met.

Intervention3：FXB0871BIOLOGICAL

Intervention4：FXB0871BIOLOGICAL

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consent. * Age ≥18 years. * Histologically confirmed selected locally advanced or metastatic solid tumor with progression on, intolerance to, or no suitable standard therapy. * ECOG performance status 0 or 1. * At least one measurable lesion per RECIST v1.1. * Pretreatment tumor tissue available (archival or fresh biopsy). * Life expectancy ≥12 weeks. * Oxygen saturation ≥92% on room air. * Left ventricular ejection fraction \>50%. * Adequate hematologic, coagulation, renal, hepatic, and cardiac function. * Women of childbearing potential and sexually active men must use highly effective contraception. * Tumor-specific eligibility applies, including prior anti-PD-(L)1 treatment failure for the selected cohorts. Key Exclusion Criteria: * Systemic anti-cancer therapy, major surgery, or radical radiotherapy within 4 weeks before first dose. * Prior treatment with IL-2, IL-15, or IL-7. * Active autoimmune disease requiring systemic treatment or immunodeficiency. * Systemic corticosteroids (≥10 mg/day prednisone equivalent) or other immunosuppressive therapy within 28 days before first dose, with limited protocol-defined exceptions. * Active or untreated central nervous system metastases, carcinomatous meningitis, or leptomeningeal disease. * Uncontrolled infection or clinically significant unresolved toxicities from prior therapy. * Clinically significant cardiovascular/cerebrovascular disease, uncontrolled effusions/ascites, uncontrolled hypertension, or QTcF \>470 ms. * Active hepatitis B/C, syphilis, or HIV infection. * Clinically significant interstitial lung disease or active noninfectious pneumonitis. * Pregnancy or breastfeeding. * Any other serious medical or psychiatric condition that, in the investigator's judgment, would make participation inappropriate.

Outcomes

Primary Outcomes

Incidence and severity of dose-limiting toxicities (DLTs) in Phase Ia

Percentage of participants with protocol-defined DLTs during the DLT observation period in the dose-escalation phase

Time frame: First 2 cycles after first dose (each cycle = 14 days; approximately 28 days).

Incidence and severity of adverse events (AEs), serious adverse events (SAEs), AEs leading to dose delay/interruption/reduction/treatment discontinuation in Phase Ia

Safety assessed by the incidence of treatment-emergent adverse events, serious adverse events, AEs leading to dose delay/interruption/reduction/treatment discontinuation in Phase Ia.

Time frame: From first dose through 90 days after last dose or initiation of new anti-tumor therapy, whichever occurs first

Objective response rate (ORR) in Phase Ib

ORR defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 in Phase Ib.

Time frame: From first dose until disease progression, start of new anti-tumor therapy, withdrawal, death, or end of study (assessed every 8±1 weeks; approximately up to 24 months).

Secondary Outcomes

Objective response rate (ORR) in Phase Ia

Objective response rate (ORR), defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR), as assessed per RECIST v1.1 in Phase Ia.

Time frame: From first dose until disease progression, start of new anti-tumor therapy, withdrawal, death, or end of study, whichever occurs first (tumor assessments every 8 ± 1 weeks; approximately up to 24 months).

Disease control rate (DCR) in Phase Ia

Disease control rate (DCR), defined as the proportion of participants with a best overall response of CR, PR, or stable disease (SD), as assessed per RECIST v1.1 in Phase Ia.

Duration of response (DOR) in Phase Ia

Duration of response (DOR), defined for participants with confirmed CR or PR as the time from first documented response to first documented disease progression or death from any cause, whichever occurs first, as assessed per RECIST v1.1 in Phase Ia.

Time frame: From first documented CR or PR until first documented disease progression or death from any cause, whichever occurs first (approximately up to 24 months).

Progression-free survival (PFS) in Phase Ia

Progression-free survival (PFS), defined as the time from first dose to first documented disease progression or death from any cause, whichever occurs first, as assessed per RECIST v1.1 in Phase Ia.

Time frame: From first dose until first documented disease progression or death from any cause, whichever occurs first (approximately up to 24 months).

Peak serum concentration (Cmax)

Maximum observed concentration