This is a multicenter, open-label, Phase Ib/II clinical study evaluating the safety, efficacy, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profiles of HS-10516 in combination with lenvatinib in patients with advanced clear cell renal cell carcinoma (ccRCC) who have progressed after receiving at least one prior line of systemic therapy. The study comprises two distinct phases: a dose exploration phase and a proof-of-concept phase.
The study will commence with a dose exploration phase employing a safety lead-in approach. Treatment cycles are set at 28 days, with investigational product administration continuing until disease progression or meeting other treatment discontinuation criteria. Each dose level will enroll 3-6 participants for dose-limiting toxicity (DLT) assessment to evaluate the tolerability, safety, and PK/PD profiles of HS-10516 combined with lenvatinib. The Safety Review Committee (SRC) will determine subsequent dose levels for exploration through joint deliberation. If all predefined dose levels prove intolerable, the SRC may authorize exploration of lower dose levels. Additionally, PK expansion cohorts (up to 12 participants per cohort) may be implemented in suitable dose levels. Following identification of safe dose levels in the exploration phase, 1-2 dose cohorts will advance to the proof-of-concept phase, with each cohort enrolling up to 40 participants to further assess therapeutic efficacy and safety.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
104
Administered orally.
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGPhase Ib: MTD or RP2D
MTD or RP2D was determined by number of participants with DLT in dose levels. A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).
Time frame: Up to 3 months
Phase II: Objective Response Rate (ORR)
The percentage of patients who have achieved complete response and partial response, according to response evaluation criteria in solid tumors (RECIST) 1.1 by investigator's assessment.
Time frame: Up to 12 months.
Incidence and severity of treatment-emergent adverse events
Incidence of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: Up to 36 months.
Disease control rate (DCR)
The percentage of patients who have achieved complete response, partial response, and stable disease, according to response evaluation criteria in solid tumors (RECIST) 1.1 by investigator's assessment.
Time frame: Up to 24 months.
Duration of response (DoR)
The time from complete or partial response to disease progression or death, according to response evaluation criteria in solid tumors (RECIST) 1.1 by investigator's assessment.
Time frame: Up to 24 months.
Progression-free survival (PFS)
Progression free survival is defined as the duration of time from study entry to time of progression, death, or is censored at date of last disease assessment.
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Time frame: Up to 24 months.
Overall survival (OS)
Overall survival is defined as the duration of time from study entry to death or the date of last contact.
Time frame: Up to 3 years.
Maximum plasma concentration (Cmax)
Cmax is defined as maximum observed serum concentration obtained directly from the observed concentration-time data.
Time frame: Up to 24 months.
Time of maximum concentration (Tmax)
Tmax is defined as the time required for a drug to reach peak concentration in plasma.
Time frame: Up to 24 months.
AUC0-t
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration.
Time frame: Up to 24 months.