Locally Advanced Solid Tumor, Metastatic Solid Tumor, Solid Cancers, Solid Tumor Cancer, Solid Tumor Malignancy, Urothelial Cancer of Renal Pelvis, Urothelial Cancer (Urinary Bladder, Ureters, or Renal Pelvis Cancer)
Conditions
Keywords
solid tumor, renal tumor, metastatic solid tumor, urothelial carcinoma
Brief summary
The goal of this study is to obtain safety, tolerability, PK, and preliminary clinical antitumor activity for XL495 as a single agent and in combination with select cytotoxic agents in participants with locally advanced or metastatic tumors for whom life-prolonging therapies do not exist or available therapies are intolerable/no longer effective.
Interventions
DRUGXL495
oral doses of XL495
DRUGADC cytotoxic agents
intravenous infusion of anti-cancer combination agent
Sponsors
Exelixis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is divided into three stages: The first stage is the dose escalation stage that evaluates how much of XL495 alone patients can safely tolerate. The second is the dose finding stage that evaluates how much of XL495 to give patients in combination with other anti-cancer medications. The third stage is the expansion stage that evaluates how XL495 performs in patients in combination with other anti-cancer medications.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For All Participants * Have received at least one standard therapy unless it does not exist, or available therapies are intolerable or no longer effective. * For participants, who qualify for approved molecularly selected therapies such as RAS inhibitors, they must have progressed on, relapsed from, been intolerant to, ineligible, or refused those therapies. * Expansion Stage * Diagnosis of metastatic advanced UC (primary tumor: renal pelvis, ureter, urinary bladder, or urethra). * At least one measurable lesion as defined by RECIST, version 1.1. * Participants must be eligible for sacituzumab govitecan treatment as their next line of therapy. * At least one but no more than 3 prior lines of therapy. * Eastern Cooperative Oncology Group (ECOG) Performance Status (0-2 for monotherapy; 0-1 for combo)
Exclusion criteria
* Prior anticancer treatment, including: * Radiation therapy within 2 weeks before first dose of study treatment. * Known brain metastases or cranial epidural disease * Current or recent severe illness * Known history or positive test for human immunodeficiency virus (HIV) unless meets specific criteria. * Active infection with hepatitis B virus or hepatitis C virus. * Malabsorption syndrome. * History of solid organ, autologous or allogenic stem cell transplant. * Diagnosis of another cancer within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with standard therapy. * Active autoimmune disease with skin involvement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-escalation and Dose-finding Stages: Number of Participants with Treatment-Emergent Adverse Events | Up to 18 months | — |
| Dose-escalation and Dose-finding Stages: Number of Participants with Dose-limiting Toxicities | Up to 18 months | — |
| Expansion Stage: Number of Participants with Treatment-Emergent Adverse Events | Up to 19 months | — |
| Expansion Stage: Objective Response Rate (ORR) As Assessed by Investigator Per RECIST 1.1 | Until disease progression or death, up to approximately 19 months | ORR is defined as the percentage of participants with the best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as assessed by the Investigator per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose-escalation and Dose-finding Stages: PK Parameter Apparent Clearance with Oral Administration of XL495 (CL/F) | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Dose-escalation and Dose-finding Stages: PK Parameter Apparent Terminal Elimination Half-life of XL495 (t1/2) | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Expansion Stage: Duration of Response (DOR) As Assessed by Investigator per RECIST 1.1 | Until disease progression or death, up to approximately 19 months. | DOR is defined as the time from the first documented objective response (CR or PR) until the earlier of radiographic progressive disease (PD) as assessed by the investigator per RECIST 1.1 or censoring due to lack of these events or start of non-protocol anti-cancer therapy. |
| Expansion Stage: Progression-free Survival (PFS), as Assessed by Investigator per RECIST 1.1 | Until disease progression or death, up to approximately 19 months. | PFS is defined as the time from start of study treatment to the earlier of either radiographic PD per RECIST 1.1 or death from any cause. |
| Expansion Stage: Concentration of XL495 in Plasma | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Dose-escalation and Dose-finding Stages: Concentration of XL495 in Plasma | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Expansion Stage: PK Parameter Maximum Plasma Concentration of XL495 (Cmax) | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Expansion Stage: PK Parameter Time to Cmax of XL495 (Tmax) | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Expansion Stage: PK Parameter Apparent Clearance with Oral Administration of XL495 (CL/F) | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Expansion Stage: PK Parameter Apparent Terminal Elimination Half-life of XL495 (t1/2) | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Expansion Stage: Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Time Curve (AUC) of XL495 | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Dose-escalation and Dose-finding Stages: Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Time Curve (AUC) of XL495 | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Dose-escalation and Dose-finding Stages: PK Parameter Maximum Plasma Concentration of XL495 (Cmax) | Pre-dose and multiple post-dose time points, up to 18 months | — |
| Dose-escalation and Dose-finding Stages: PK Parameter Time to Cmax of XL495 (Tmax) | Pre-dose and multiple post-dose time points, up to 18 months | — |
Countries
United States
Outcome results
None listed