Study of the Combination of CM082 With Everolimus in Patients With mRCC

This is a Phase I Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CM082 in Combination with Everolimus in Chinese Patients With Renal Cell Carcinoma (RCC). After the maximum tolerated dose (MTD) or the optimal biological dose is identified, an expansion cohort of \~10 advanced renal cell carcinoma patients will be enrolled to further characterize the safety and tumor response by CT.

• CM082 (Drug), also known as X-82: CM082 tablets taken orally once a day on 28-day cycles
• Everolimus (Drug), also known as Affinitor: Everolimus tablets taken orally once a day on 28-day cycles

Primary outcomes

• Maximum Tolerated Dose [12 months]: To determine the Maximum Tolerated Dose of the Combination in Chinese RCC Patients

Secondary outcomes

• Pharmacokinetics assessed by area under the plasma concentration versus time curve (AUC) of CM082 and everolimus [12 months]
• Objective response rate [18 months]: Objective response rate (ORR)
• Progress free survival [24 months]: Progress free survival (PFS)

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of clear cell renal cell carcinoma
* Progressed on at least one standard therapy
* Measurable disease per Recist1.1
* Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1
* Life expectancy of at least 12 weeks
* No abnormal bone marrow function
* Adequate heart, lung, liver, kidney organ system functions, and meet the following requirements:

  * Total bilirubin ≤1.5 times the upper limit of normal (ULN)
  * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5x the upper limit of normal (ULN) if no liver involvement or ≤5x the upper limit of normal with liver involvement.
  * Creatinine ≤ 1.5 x ULN
  * Urine protein <1+
  * QTcF < 450 ms
  * LVEF ≥ 50%
* At least 4 weeks after receiving cancer therapy (i.e., chemotherapy, radiation therapy, biologic therapy, hormonal therapy); 3 months after surgery and recovered
* Willingness and ability to comply with trial and follow-up procedures
* Ability to understand the nature of this trial and give written informed consent

Exclusion Criteria:

* Currently receiving anti-cancer treatment
* Other tumors in addition to renal cell carcinoma
* Have taken strong cytochrome P450 3A4 inhibitors or inducers in the last 2 weeks
* Concomitant use of drugs with a risk of causing prolonged corrected QT interval and/or Torsades de Pointes
* Patients with a history of intolerance to, or significant toxicity with VEGFR tyrosine kinase inhibitor(s) (TKI) or everolimus
* Females who are pregnant or breastfeeding
* Those in reproductive ages who refuse to use contraception
* Those with concurrent condition(e.g. psychological, neuronal, cardiovascular, respiratory conditions or infections) that in the investigator's opinion would jeopardize compliance with the protocol
* Patients with known central nervous system (CNS) metastases
* Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of CM082 or everolimus
* Patients with known severe lung disorders such as asthma, chronic obstructive pulmonary disease (COPD)
* Patients who are HIV positive
* Drug or alcohol abuser

• Jun Guo, M.D, Study chair, Peking University Cancer Hospital & Institute
• Xinan Sheng, M.D, Principal investigator, Peking University Cancer Hospital & Institute