Clinical Trial 21105

• Overview

  Study Title:

  A Randomized, Double-blind, Placebo-controlled, Phase 2 Study of INBRX-109 as Any-line Therapy in Conventional Chondrosarcoma

  Summary:

  This is a randomized, blinded, placebo-controlled, Phase 2 study of INBRX-109 in unresectable or metastatic conventional chondrosarcoma patients. INBRX-109 is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).

  Objective:

  1. To evaluate the anticancer efficacy of INBRX-109 in the intention-to-treat (ITT) population as measured by progression free survival (PFS) per RECISTv1.1, assessed by central independent radiology review (IRR), comparing INBRX-109 and placebo; 2. To evaluate the anticancer efficacy of INBRX-109 as measured by overall survival (OS) comparing INBRX-109 and placebo; 3. To evaluate the anticancer efficacy of INBRX-109 as measured by objective response rate (ORR) per RECISTv1.1, assessed by central IRR, comparing INBRX-109 and placebo; 4. To evaluate duration of response (DOR) per RECISTv1.1, assessed by central IRR, comparing INBRX-109 and placebo; 5. To evaluate the anticancer efficacy of INBRX-109 as measured by disease control rate (DCR) per RECISTv1.1, assessed by central IRR, comparing INBRX-109 and placebo. 6. To evaluate the anticancer efficacy of INBRX-109 as measured by PFS per RECISTv1.1, by Investigator assessment, comparing INBRX-109 and placebo; 7. To evaluate quality of life (QoL), comparing INBRX-109 and placebo (i.e., EORTC QLQ-C30); 8. To evaluate the safety and tolerability of INBRX-109; 9. To characterize the pharmacokinetics of INBRX-109; 10. To evaluate the frequency of anti-drug antibodies (ADA), and neutralizing ADA (NAb), against INBRX-109 and to explore the potential relationship with safety, pharmacokinetics and efficacy of INBRX-109.

• Treatments

  Therapies:

  Immunotherapy; Therapy (NOS)

  Medications:

  INBRX-109 (); Placebo ()

• Inclusion Criteria

  Inclusion Criteria:
  • Males or females between 18 and 85 years of age. Note: potential inclusion of patients who are chronologically older than 85 years, but with ECOG 0 and a younger biologic age per comprehensive geriatric assessment, must be based on discussion with the Medical Monitor or Study Director
  • Conventional chondrosarcoma, unresectable (=inoperable) or metastatic.
  • Measurable disease by RECISTv1.1. Note: Tumor lesions located in a previously irradiated (or other locally treated) area will be considered measurable, provided there has been clear imaging-based progression of the lesions since the time of treatment.
  • Radiologic progression of disease per RECISTv1.1 criteria within 6 months prior to screening for this study.
  • Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.Exception: non-frail, physically active patients with compromised mobility due to prior cancer surgery (e.g. limb amputation, hemipelvectomy etc) should be discussed with the Medical Monitor or Study Director.
  • Estimated life expectancy, in the documented judgment of the Investigator, of at least 12 weeks.
  • Availability of archival tissue or fresh cancer biopsy are mandatory. Note: A confirmation of IDH mutational status (per CLIA-certified assay or equivalent) is required for stratification prior to randomization, any status is allowed, i.e. IDH1, IDH2 or wildtype.
  • Other criteria apply

• Exclusion Criteria

  Exclusion Criteria:
  • Any prior exposure to DR5 agonists. z,,8..t eceipt of any anti-cancer therapy (including investigational agents) within 4 weeks or within 5 half-lives prior to the first dose of study treatment whichever is shorter. Note: patients who received pazopanib as an immediate prior line, must have a 4 week washout and no evidence of prior or residual hepatotoxicity. Note: patients with any history or evidence of Grade ≥3 hepatotoxicity on prior anti-cancer therapy are excluded
  • Receipt of radiotherapy (with the exception of palliative localized radiation) within 4 weeks to the first dose of study treatment. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.  Note: 1-week washout is required for palliative radiation to non-CNS disease. Note: patients who had prior radiotherapy involving the liver (total calculated dose to the liver >10Gy) are excluded
  • Receipt of liver-directed therapies (e.g., Radio frequency ablation (RFA), trans-arterial chemoembolization (TACE), radioembolization, cryotherapy, Stereotactic Body Radiation Therapy (SBRT), or others) within 12 months prior to the first dose of study treatment. Note: patients who had prior radioembolization with Yttrium-90 beads are excluded
  • Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
  • Non-conventional chondrosarcoma, e.g., clear-cell, mesenchymal, extraskeletal myxoid, myxoid, and dedifferentiated chondrosarcoma.
  • Prior or concurrent malignancies. Exception: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments.
  • Chronic liver diseases. Exception: Patients with fatty liver disease are acceptable as long as adequate hepatic function as defined in the inclusion criteria is confirmed.
  • Other exclusions apply

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