Clinical Trials /

Study of XL102 as Single-Agent and Combination Therapy in Subjects With Solid Tumors

NCT04726332

Description:

This is a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, PK, antitumor activity, and effect on biomarkers of XL102 administered orally alone and in multiple combination regimens to subjects with advanced solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of XL102 as Single-Agent and Combination Therapy in Subjects With Solid Tumors
  • Official Title: A Dose Escalation and Expansion Study of the Safety and Pharmacokinetics of XL102 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: XL102-101
  • NCT ID: NCT04726332

Conditions

  • Neoplasm Malignant
  • Epithelial Ovarian Cancer
  • Triple Negative Breast Cancer
  • Hormone Receptor Positive Breast Carcinoma
  • Metastatic Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
XL102XL102 + Abiraterone/Prednisone Dose-Escalation Cohorts
FulvestrantXL102 + Fulvestrant Dose-Escalation Cohorts
AbirateroneXL102 + Abiraterone/Prednisone Dose-Escalation Cohorts
PrednisoneXL102 + Abiraterone/Prednisone Dose-Escalation Cohorts

Purpose

This is a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, PK, antitumor activity, and effect on biomarkers of XL102 administered orally alone and in multiple combination regimens to subjects with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
XL102 Single-Agent Dose-Escalation CohortsExperimentalSubjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
  • XL102
XL102 Single-Agent Expansion CohortsExperimentalThe MTD or recommended dose from the dose-escalation stage may be further explored in subjects with triple-negative breast cancer (TNBC) (Cohort D), epithelial ovarian cancer (EOC) (Cohort E), hormone receptor-positive breast cancer (HR+ BC) (Cohort F), and metastatic castration-resistant prostate cancer (mCRPC) (Cohort G).
  • XL102
XL102 + Fulvestrant Dose-Escalation CohortsExperimentalSubjects with HR+ BC (Cohort B) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
  • XL102
  • Fulvestrant
XL102 + Abiraterone/Prednisone Dose-Escalation CohortsExperimentalSubjects with mCRPC (Cohort C) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.
  • XL102
  • Abiraterone
  • Prednisone
XL102 + Fulvestrant Expansion CohortsExperimentalThe MTD or recommended dose from the dose-escalation stage may be further explored in subjects with HR+ BC (Cohort H).
  • XL102
  • Fulvestrant
XL102 + Abiraterone/Prednisone Expansion CohortsExperimentalThe MTD or recommended dose from the dose-escalation stage may be further explored in subjects with mCRPC (Cohort I).
  • XL102
  • Abiraterone
  • Prednisone

Eligibility Criteria

        Inclusion Criteria:

          -  Cytologically or histologically and radiologically confirmed solid tumor that is
             inoperable, locally advanced, metastatic, or recurrent.

          -  Dose-Escalation Stage Cohort A (Solid Tumors): The subject has a solid tumor that is
             unresectable or metastatic and for which life-prolonging measures do not exist or
             available therapies are intolerable or no longer effective.

          -  Dose-Escalation Stage Cohort B and Cohort-Expansion Stage Cohorts F and H (Hormone
             Receptor-Positive Breast Cancer): Subjects with breast cancer that is hormone
             receptor-positive (estrogen receptor positive [ER+] and/or progesterone receptor
             positive [PR+]) and negative for human epidermal growth factor receptor 2 (HER-2
             negative [HER-2-]) and who have documented radiographic disease progression during or
             following their last systemic anticancer therapy for inoperable locally advanced or
             metastatic disease.

          -  Dose-Escalation Stage Cohort C and Cohort-Expansion Stage Cohorts G and I (Metastatic
             Castration-Resistant Prostate Cancer): Subjects with adenocarcinoma of the prostate.
             Note: Neuroendocrine differentiation and other histological features are permitted if
             adenocarcinoma is the primary histology.

          -  Cohort-Expansion Stage Cohort D (Triple Negative Breast Cancer): Subjects with breast
             cancer that is negative for HER-2, estrogen receptors, and progesterone receptors, and
             who have documented radiographic disease progression during or following their last
             systemic anticancer therapy for inoperable locally advanced or metastatic disease.

          -  Cohort-Expansion Stage Cohort E (Epithelial Ovarian Cancer): Subjects with epithelial
             ovarian cancer, including primary peritoneal cancer (PPC) and fallopian tube cancer
             (FTC) who have platinum-resistant disease following treatment with a
             platinum-containing chemotherapy. Ovarian borderline epithelial tumors (low malignant
             potential) are excluded.

          -  Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1 as determined
             by the Investigator.

          -  Tumor tissue material (archival or fresh tumor tissue [if it can be safely obtained]).

          -  Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse
             Events version 5 [CTCAE v5]) from AEs.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.

          -  Adequate organ and marrow function.

          -  Sexually active fertile subjects and their partners must agree to use medically
             accepted methods of contraception.

          -  Female subjects of childbearing potential must not be pregnant at screening.

        Exclusion Criteria:

          -  Receipt of XL102 or any other selective CDK7 inhibitor.

          -  Receipt of any cytotoxic chemotherapy therapy or anticancer antibody therapy within 21
             days before first dose of study treatment.

          -  Receipt of any type of small molecule kinase inhibitor within 2 weeks before first
             dose of study treatment.

          -  Receipt of any anticancer hormonal therapy within 2 weeks or within 5 half-lives of
             the agent, whichever is shorter, before first dose of study treatment.

          -  HR+BC subjects enrolled in the Combination Cohorts B and H receiving fulvestrant prior
             to first dose of study treatment are allowed to continue with their fulvestrant
             treatment.

          -  Metastatic CRPC subjects enrolled in the Combination Cohorts C and I receiving
             abiraterone prior to first dose of study treatment are allowed to continue with their
             abiraterone treatment.

          -  Radiation therapy within 14 days before first dose of study treatment. Subjects with
             clinically relevant ongoing complications from prior radiation therapy are not
             eligible.

          -  Known brain metastases or cranial epidural disease unless adequately treated with
             radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks
             before first dose of study treatment.

          -  Concomitant use of certain medications.

          -  Uncontrolled, significant intercurrent or recent illness.

          -  Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per
             electrocardiogram (ECG).

          -  Pregnant or lactating females.

          -  Diagnosis of another malignancy 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 systemic therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-Escalation Stage: MTD/recommended dose for XL102
Time Frame:Approximately 18 months
Safety Issue:
Description:To determine the MTD and/or RD for further evaluation of XL102 when administered orally alone and in combination therapy in subjects with advanced solid tumors

Secondary Outcome Measures

Measure:Safety of XL102 as evaluated by Incidence and Severity of Adverse Events (AEs)
Time Frame:Approximately 30 months
Safety Issue:
Description:To evaluate the safety of XL102 when administered orally alone and in combination therapy through the evaluation of overall incidence of AEs, severity grade, relationship to study treatment, and laboratory tests.
Measure:Tolerability of XL102 as evaluated by Study Treatment Exposure, Dose Intensity and Modifications, and Study Treatment Discontinuation due to AE
Time Frame:Approximately 30 months
Safety Issue:
Description:To evaluate the tolerability of XL102 when administered orally alone and in combination therapy through the evaluation of study treatment exposure, dose intensity, dose modifications, and study treatment discontinuation due to AE.
Measure:Dose-Escalation Stage: Drug-Drug Interactions
Time Frame:Approximately 18 months
Safety Issue:
Description:To assess drug-drug interactions between XL102 and combination agents
Measure:Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)
Time Frame:Approximately 18 months
Safety Issue:
Description:To evaluate the Tmax of XL102 alone and in combination therapy
Measure:Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)
Time Frame:Approximately 18 months
Safety Issue:
Description:To evaluate the Cmax of XL102 alone and in combination therapy
Measure:Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24)
Time Frame:Approximately 18 months
Safety Issue:
Description:To evaluate the AUC 0-24 of XL102 alone and in combination therapy
Measure:Dose-Escalation Stage: Terminal Half-Life
Time Frame:Approximately 18 months
Safety Issue:
Description:To evaluate the terminal half-life of XL102 alone and in combination therapy
Measure:Dose-Escalation Stage: Apparent Clearance (CL/F)
Time Frame:Approximately 18 months
Safety Issue:
Description:To evaluate the CL/F of XL102 alone and in combination therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Exelixis

Last Updated

May 10, 2021