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Brief Title: XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors

A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL092 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors

INTRODUCTION

  • Org Study ID: XL092-001
  • Secondary ID: N/A
  • NTC ID: NCT03845166
  • Sponsor: Exelixis

BRIEF SUMMARY

This is a Phase 1, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect on biomarkers of XL092 administered alone, in combination with atezolizumab, and in combination with avelumab to subjects with advanced solid tumors.

  • Overall Status
    Recruiting
  • Start Date
    March 20, 2019
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Dose-Escalation Stage: MTD/recommended dose for XL092

Primary Outcome 1 - Timeframe: Up to 24 months

Primary Outcome 2 - Measure: Cohort-Expansion Stage: Objective Response Rate (ORR)

Primary Outcome 2 - Timeframe: Up to 24 months

Primary Outcome 3 - Measure: Cohort-Expansion Stage: Progression-Free Survival (PFS)

Primary Outcome 3 - Timeframe: Up to 24 months

CONDITION

  • Neoplasm Malignant
  • Renal Cell Carcinoma
  • Hormone Receptor Positive Breast Carcinoma
  • Metastatic Castration-resistant Prostate Cancer
  • Urothelial Carcinoma
  • Colorectal Cancer

ELIGIBILITY

Inclusion Criteria:
Cytologically or histologically confirmed solid tumor that is inoperable locally advanced, metastatic, or recurrent.

- Dose-escalation (single-agent and combination therapy): Subjects with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.

- Expansion Cohort A (ccRCC): Subjects with previously treated advanced RCC with clear cell histology (including those with a sarcomatoid component) who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.

- Expansion Cohorts B and E (nccRCC): Subjects with previously treated advanced RCC with non-clear cell histology who have radiographically progressed following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.

- Expansion Cohorts C and F (HR+ BC): Subjects with breast cancer that is hormone receptor positive (ER+ and/or PR+) and negative for human epidermal growth factor receptor 2 (HER-2) and who have radiographically progressed during or following treatment with at least one prior systemic anticancer regimen for inoperable locally advanced or metastatic disease.

- Expansion Cohorts D and G (mCRPC): Subjects with metastatic CRPC (adenocarcinoma of the prostate). Neuroendocrine differentiation and other features permitted if adenocarcinoma is the primary histology.

- Expansion Cohort H (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum who received prior fluoropyrimidine-containing chemotherapy with oxaliplatin or irinotecan.

- Expansion Cohort I (UC, Maintenance Therapy): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who received first-line chemotherapy of gemcitabine + cisplatin and/or gemcitabine + carboplatin.

- Expansion Cohort J (UC, ICI-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after PD-1/PD-L1 targeting ICI therapy.

- Expansion Cohort K (UC, platinum-refractory): Subjects with histologically confirmed, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra) who progressed on or after first-line platinum-based combination therapy.

- Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1, with exception of Cohort I (UC, Maintenance Therapy).
Tumor tissue material:
Subjects in the non-biomarker cohort provide archival, if available, or fresh tumor tissue if it can be safely obtained.

- Subjects in the Biomarker Cohorts provide fresh tumor and skin biopsies.

- Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.

- 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:
Prior treatment with XL092 (all cohorts), prior treatment with PD-L1/PD-1 targeting immune checkpoint inhibitor (Cohorts E, F, G, H, I, and K only) or prior avelumab (Cohort J only).

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

- Receipt of any type of anticancer antibody, systemic chemotherapy, or hormonal anticancer therapy within 4 weeks before first dose of study treatment.

- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks 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.

- Uncontrolled, significant intercurrent or recent illness.

- Concomitant use of certain medications.

- Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within 10 days per electrocardiogram (ECG) before first dose of study treatment.

- 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.
Additional Exclusion Criteria for XL092 + Atezolizumab Combination Therapy Cohorts ONLY:
Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 2 weeks prior to first dose of study treatment.

- Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.
Additional Exclusion Criteria for XL092 + Avelumab Combination Therapy Cohorts ONLY:
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent.

- Administration of a live, attenuated vaccine within 30 days before first dose of study treatment.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 1-888-EXELIXIS (888-393-5494), 650-837-7400

Email: druginfo@exelixis.com

LOCATION

Facility Status Contact
Facility: Exelixis Clinical Site #6
Duarte, California 91010
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #7
Los Angeles, California 90025
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #4
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #2
Grand Rapids, Michigan 49546
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #3
Houston, Texas 77030
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #1
San Antonio, Texas 78229
United States
Status: Recruiting Contact: N/A
Facility: Exelixis Clinical Site #5
Salt Lake City, Utah 84112
United States
Status: Recruiting Contact: N/A