HS-10516 plus lenvatinib for advanced clear-cell kidney cancer

A Phase Ib/II Clinical Study Evaluating the Safety, Efficacy, Tolerability, and Pharmacokinetics of HS-10516 Combination Therapy in Patients With Advanced Renal Cell Carcinoma

This study will test whether adding HS-10516 to lenvatinib helps adults with advanced clear-cell kidney cancer who have progressed after at least one prior systemic treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 104 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: lenvatinib, chemotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07097935 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase Ib/II study gives HS-10516 in combination with lenvatinib to adults with advanced clear-cell renal cell carcinoma who progressed after ≥1 prior systemic therapy. It begins with a dose-exploration safety lead-in using 28-day treatment cycles where 3–6 participants per dose level are enrolled to monitor dose-limiting toxicities and PK/PD. A Safety Review Committee will decide dose escalation or de-escalation and PK expansion cohorts (up to 12 participants each) may be added at suitable dose levels. After safe dose levels are identified, one or two dose cohorts will move to a proof-of-concept Phase II stage enrolling up to 40 participants per cohort to further test efficacy and safety until disease progression or other discontinuation criteria are met.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable or metastatic clear-cell RCC who have progressed after at least one prior systemic therapy, have measurable disease per RECIST 1.1, ECOG 0–1, and an estimated life expectancy >12 weeks.

Not a fit: Patients with non–clear-cell histology, only brain or bone target lesions, ECOG performance status >1, or major comorbidities that preclude study treatments are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could provide an additional treatment option that prolongs disease control for patients with advanced ccRCC after prior therapies.

How similar studies have performed: Lenvatinib combinations have shown activity in RCC in prior studies, but HS-10516 is investigational and this specific combination is exploratory.

Eligibility criteria

Inclusion Criteria:

1. Men or women aged more than or equal to (≥) 18 years.
2. Histologically confirmed unresectable, locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) with disease progression during or after receiving ≥1 prior line of systemic therapy in the advanced setting.
3. Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required). Patients with only brain and/or bone lesions as target lesions will not be included.
4. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
5. Estimated life expectancy greater than (\>) 12 weeks.
6. Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 12 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
7. Females must have the evidence of non-childbearing potential
8. Sign informed consent form.

Exclusion Criteria:

1. Prior or Current Treatments:

   1. Previous or current use of hypoxia-inducible factor inhibitors.
   2. Previous or current use of lenvatinib.
   3. Use of Chinese herbal medicine with antitumor indications within 2 weeks prior to the first dose or requirement for such treatment during the study.
   4. Administration of cytotoxic chemotherapy or other systemic antitumor therapies (e.g., endocrine therapy, molecular targeted therapy) within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose, or requirement for such treatments during the study.
   5. Use of large-molecule antitumor drugs within 4 weeks prior to the first dose or requirement for such treatment during the study.
   6. Use of CYP2C19 strong inhibitors/inducers or narrow therapeutic index sensitive substrates within 7 days prior to the first dose, or requirement for continued use during the study.
   7. Local radiotherapy (except brain radiotherapy; see Criterion 6) within 2 weeks prior to the first dose, or \>30% bone marrow irradiation/large-field radiotherapy within 4 weeks prior to the first dose.
   8. Major surgery (e.g., craniotomy, thoracotomy, laparotomy; Grade 3/4 per Chinese Medical Technical Clinical Application Regulations) within 4 weeks prior to the first dose.
   9. Participation in other interventional clinical trials within 4 weeks prior to the first dose or within 5 half-lives of investigational drugs (whichever is longer).
2. Resting pulse oximetry \<92% at screening.
3. Severe pulmonary dysfunction requiring intermittent/long-term oxygen therapy.
4. Unresolved Grade \>1 toxicities from prior anti-tumor therapy (per CTCAE v5.0).
5. History of second primary malignancy.
6. Known or suspected active CNS metastases/leptomeningeal disease.
7. Inadequate bone marrow reserve or serious organ dysfunction.
8. Severe, uncontrolled, or active cardiovascular disease.
9. Severe or poorly controlled diabetes.
10. Severe or poorly controlled hypertension.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jun Guo

Conditions Advanced Clear Cell Renal Cell Carcinoma