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

Official title

A Phase 1a/1b Open-Label, Multicenter, Dose Escalation, and Dose Expansion Trial to Evaluate the Safety, Anti-tumor Activity, Pharmacokinetic/Pharmacodynamic Characteristics of FXB0871 as Monotherapy in Participants With Selected Locally Advanced or Metastatic Solid Tumors

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.

Detailed description

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.

Interventions

• Biological Intervention1：FXB0871
  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.
• Biological Intervention2：FXB0871
  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.
• Biological Intervention3：FXB0871
  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.
• Biological Intervention4：FXB0871
  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.

Primary outcome measures

• Incidence and severity of dose-limiting toxicities (DLTs) in Phase Ia [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 [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 [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 outcome measures (12)

• Objective response rate (ORR) 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 [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).]
• Duration of response (DOR) 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 [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) [Time frame: Predose up to Day 8]
• Time to maximum observed concentration (Tmax) [Time frame: Predose up to Day 8]
• Area under the serum concentration-time curve (AUC0-last) [Time frame: Predose up to Day 8]
• Area under the serum concentration-time curve (AUC0-∞) [Time frame: Predose up to Day 8]
• Area under the serum concentration-time curve (AUCtau) [Time frame: Predose up to Day 8]
• Trough concentration (Ctrough) [Time frame: up to Day 8]
• Clearance (CL) [Time frame: Predose up to Day 8]
• Volume of distribution (Vz) [Time frame: Predose up to Day 8]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai East Hospital — Shanghai

Identifiers

NCT: NCT07558200 · FXB0871-I101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗