Trial Search Results

A Study of XL092 as Single-Agent and Combination Therapy in Subjects With Solid Tumors

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Exelixis

Stanford Investigator(s):

Intervention(s):

  • Drug: XL092
  • Drug: Atezolizumab
  • Drug: Avelumab

Phase:

Phase 1

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, KRAS/NRAS wild-type
   (confirmed via local testing report) and determined NOT to have microsatellite
   instability high (MSI-high) or mismatch repair deficient (dMMR) by local testing, who
   received the following standard of care chemotherapy regimens as prior therapy for
   metastatic CRC:

      - Fluoropyrimidine, irinotecan and oxaliplatin, with or without an anti-VEGF
      monoclonal antibody (bevacizumab)

      - Anti-EGFR monoclonal antibody (cetuximab or panitumumab)

      - BRAF inhibitor (in combination with cetuximab +/- binimetinib) for subjects with
      BRAF V600E mutations

   - 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.

   - Recovery to baseline or ‚ȧ 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 highly effective
   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), prior treatment with
   avelumab (Cohort J only), or prior treatment with regorafenib and/or TAS-102 (Cohort H
   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) > 450 ms for males
   and > 470 ms for females. Single ECGs are no longer permitted.

   - 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.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Paige Nicole Baker
+1 650-736-1252
Recruiting