Clinical Trial 21117

• Overview

  Study Title:

  A Phase 1 Multicenter Study Evaluating the Safety and Efficacy of ALLO-316 Following ALLO-647 Containing Conditioning Regimen in Subjects with Advanced or Metastatic Clear Cell Renal Cell Carcinoma (ccRCC)

  Summary:

  he purpose of the TRAVERSE study is to assess the safety, efficacy, and cell kinetics of ALLO-316 in adults with advanced or metastatic clear cell renal cell carcinoma after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647 to define a Phase 2 dose.

  Objective:

  Primary Objectives: -to assess safety and tollerability at increasing dose levels of ALLO-316 in successive cohorts of subjects with advanced or metastatic ccRCC to estimate the maximum tolerated dose (MTD) of ALLO-316 administered following conditioning with fludarabine/cyclophosphamide (Flu/Cy) and ALLO-647 and to select the recommended Phase 2 dose (RP2D) of ALLO-316. -to assess safety and tolerability of ALLO-647 in combination with Flu/Cy prior to ALLO-316 and to establish the RP2D of ALLO-647. Secondary Objectives -to evaluate the overall safety provile of ALLO-316 following ALLO-647 in combination with Flu/Cy. -to evaluate anti-tumor activity of ALLO-316 -to characterize cellular kinetics of ALLO-316 to characterize the pharmacokinetics of ALLO-647 -to evaluate immunogenicity against ALLO-316 and ALLO-647 -to evaluate correlation of clinical outcomes with CD70 expression Exploratory Objectives: -to explore potential biomarker development based on assessment of blood cells and tumor cells for ALLO-316 and ALLO-647 -to explore changes in immunoregulatory transcripts (RNA profile) and T cell clonal diversity (TCR DNA sequencing) and its relationship to ALLO-316 expansion, persistence, and activity -to explore the impact of ALLO-316 on systemic soluble immune factors -to collect banked biospecimens for exploratory research, unless prohibited by local regulations or ethics committee decision -to evaluate host immune cell depletion and reconstitution resulting from condition with ALLO-647 in combination with Flu/Cy prior to ALLO-316 -to describe the preliminary antitumor activity of ALLO-316 in subjects with ccRCC based on immune-related RECIST (irRECIST) criteria -to explore the safety and efficacy of retreatment with ALLO-316

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  ALLO-316 (); ALLO-647 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  • Histologically confirmed, CD70 positive (by CLIA-validated IHC assay) renal cell carcinoma with a predominant clear cell component. CD-70 positive is determined using a centrally performed IHC assay.
  • For CD70 IHC, an archival representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or a minimum of 15 unstained, freshly cut, serial sections from an FFPE tumor specimen obtained within 12 months of screening is required. For patients who consent and undergo a fresh biopsy, a total of 3 core biopsies are to be obtained if possible. This specimen is preferred to be accompanied by the associated pathology report. If fewer than 15 slides are available (but no fewer than 10), the patient may still be eligible upon discussion with the study medical monitor. For core needle biopsy specimens, it is preferable to combine at least 3 cores embedded in a single paraffin block to be submitted for evaluation. If samples do not meet the minimum requirements for size/slide number, contact the study medical monitor to determine if the subject is eligible for study participation. In the setting where archival material is unavailable or unsuitable for use, patients must consent to and undergo incisional, or core tumor biopsy obtained from a low-risk anatomical site.
  • Must have received a checkpoint inhibitor and a VEGF inhibitor in the advanced and/or metastatic setting
  • At least one measurable lesion as defined by RECIST version 1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
  • Absence of significant donor (product)-specific anti-HLA antibodies (DSA)
  • Adequate hematological, renal, liver, pulmonary, and cardiac functions
  • Other criteria may apply.

• Exclusion Criteria

  • Central nervous system (CNS) metastatic disease (unless controlled and stable for at least 4 weeks), leptomeningeal disease, or cord compression
  • Clinically significant CNS dysfunction
  • Any other active malignancy within 3 years prior to enrollment
  • Prior treatment with anti-CD70 therapies
  • Current thyroid disorder (including hyperthyroidism) with the exception of hypothyroidism controlled on stable dose of hormone replacement therapy
  • Prior treatment with anti-CD52 monoclonal antibody in the past 12 months
  • Patients unwilling to participate in the extended safety monitoring period

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