A Multicenter, Open-label, Phase Ib/II Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of YL201 Combined With Toripalimab, With or Without Cisplatin, in Subjects With Recurrent or Metastatic Nasopharyngeal Carcinoma.
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 202
- Locations
- 20
- Primary Endpoint
- Number of Participants Experiencing Dose-limiting toxicities (DLTs)
Study Overview
Brief Summary
This is a multicenter, open-label, Phase Ib/II study conducted in China to evaluate the safety, efficacy, and pharmacokinetic (PK) characteristics of YL201 combined with Toripalimab (doublet regimen) or YL201 combined with Toripalimab and Cisplatin (triplet regimen) in subjects with recurrent or metastatic nasopharyngeal carcinoma.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily sign a written informed consent form (ICF).
- •Aged ≥18 years and ≤75 years, male or female.
- •ECOG performance status score of 0 or
- •Life expectancy ≥ 3 months.
- •Disease and treatment history:
- •Histologically or cytologically confirmed recurrent or metastatic nasopharyngeal carcinoma that is not amenable to curative treatment.
- •Patients with newly diagnosed advanced nasopharyngeal carcinoma, categorized as Stage IV according to the 9th Edition of the American Joint Committee on Cancer (AJCC) Staging System; or those with recurrent nasopharyngeal carcinoma deemed unsuitable for local treatment
- •Metastatic or recurrent patients who are systemic treatment naïve.
- •At least one measurable lesion according to RECIST v1.
- •Adequate organ function.
Exclusion Criteria
- •History of other malignant tumors within 5 years prior to the first dose of study drug. Subjects who have been cured of other tumors by local therapy, such as basal cell carcinoma, squamous cell carcinoma of skin, bladder cancer in situ, cervical carcinoma in situ, or breast cancer in situ, are not excluded.
- •Patients with brainstem metastases, leptomeningeal metastases, spinal cord metastases, or spinal cord compression.
- •Patients with severe, uncontrolled cardiovascular disease.
- •Patients with concomitant pulmonary disease resulting in clinically severe impairment of respiratory function.
- •History of interstitial lung disease (ILD) or non-infectious pneumonitis requiring corticosteroid therapy, OR current ILD or non-infectious pneumonitis.
- •Prior treatment with a B7-H3 targeted therapy (including antibodies, antibody-drug conjugates [ADCs], CAR-T cells, and other agents), or with a topoisomerase I inhibitor or an ADC containing a topoisomerase I inhibitor payload.
- •Prior treatment with a PD-(L)1 inhibitor (including antibodies, antibody-drug conjugates [ADCs], CAR-T cells, and other agents).
Arms & Interventions
Dose Exploration (Part 1)
To evaluate the safety and efficacy of YL201 combined with Toripalimab in subjects with recurrent or metastatic nasopharyngeal carcinoma
Intervention: YL201 (Drug)
Dose Exploration (Part 1)
To evaluate the safety and efficacy of YL201 combined with Toripalimab in subjects with recurrent or metastatic nasopharyngeal carcinoma
Intervention: Toripalimab (Drug)
Dose Exploration (Part 2)
To evaluate the safety and efficacy of YL201 combined with Toripalimab with/without Cisplatin in subjects with recurrent or metastatic nasopharyngeal carcinoma.
Intervention: YL201 (Drug)
Dose Exploration (Part 2)
To evaluate the safety and efficacy of YL201 combined with Toripalimab with/without Cisplatin in subjects with recurrent or metastatic nasopharyngeal carcinoma.
Intervention: Toripalimab (Drug)
Dose Exploration (Part 2)
To evaluate the safety and efficacy of YL201 combined with Toripalimab with/without Cisplatin in subjects with recurrent or metastatic nasopharyngeal carcinoma.
Intervention: Cisplatin (Drug)
Outcomes
Primary Outcomes
Number of Participants Experiencing Dose-limiting toxicities (DLTs)
Time Frame: Approximately within 36 months
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time Frame: Approximately within 36 months
Progression-Free Survival (PFS) as assessed by RECIST v1.1
Time Frame: Approximately within 36 months
Secondary Outcomes
- Disease Control Rate (DCR)(Approximately within 36 months)
- Objective Response Rate (ORR)(Approximately within 36 months)
- Time to Response (TTR)(Approximately within 36 months)
- Duration of Response (DoR)(Approximately within 36 months)
- Overall survival(OS)(Approximately within 36 months)
- Incidence of anti-drug antibodies (ADA) to YL201 (and to Toripalimab, if necessary)(Approximately within 36 months)
- Characterize the PK parameter AUC of YL201 and its metabolites, if applicable(Approximately within 36 months)
- Characterize the PK parameter Cmax of YL201 and its metabolites, if applicable(Approximately within 36 months)
- Characterize the PK parameter Ctrough of YL201 and its metabolites, if applicable(Approximately within 36 months)
- Characterize the PK parameter t1/2 of YL201 and its metabolites, if applicable(Approximately within 36 months)