MC# 19-08 - A Phase I Multiple-Dose Study to Evaluate the Safety and Tolerability of XmAb®23104 in Subjects with Selected Advanced Solid Tumors

  • Agent(s): XmAb23104
  • Disease Type(s): Bladder, Cervical, Colorectal, Endometrial, Gastric, Hepatocellular, Melanoma, Pancreatic, Renal, Lung-NSCLC, Lung-SCLC, Breast- Triple Negative, Nasopharyngeal, Squamous Cell Carcinoma of Head and Neck, Gastroesophageal Junction
  • Phase(s): I
  • Drug Classification(s): Bispecific Antibodies
  • Molecular Target(s): PD-1, ICOS

Mechanism of Action

XmAb23104 is an anti-PD1/ICOS bispecific monoclonal antibody. It binds to both PD-1 and ICOS expressed on certain T cells, including tumor-infiltrating lymphocytes (TILs). This prevents the activation of PD-1 and stimulates ICOS-mediated signaling, which promotes the activation of T cells and enhances T-cell-mediated immune responses against tumor cells.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of XmAb23104 can be given with an acceptable level of side effects
  • The effects of XmAb23104 (good and bad)
  • How fast XmAb23104 is removed from the blood
  • How you immune system reacts to XmAb23104
  • If research tests can be used in the future to predict who will benefit from XmAb23104
Inclusion Criteria
  • Males and females, age ≥ 18 years
  • Subjects in Part A (dose escalation) must have a diagnosis of any of the following:
    • Histologically or cytologically confirmed advanced solid tumors, including the following:
    • Melanoma (excluding uveal melanoma)
    • Cervical carcinoma
    • Pancreatic carcinoma
    • Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)
    • Hepatocellular carcinoma
    • Urothelial carcinoma
    • Squamous cell carcinoma of the head and neck (HNSCC)
    • Nasopharyngeal carcinoma (NPC)
    • Renal cell carcinoma
    • Colorectal carcinoma
    • Endometrial carcinoma
    • NSCLC
    • Small cell lung cancer
    • Gastric or gastroesophageal junction adenocarcinoma
  • Subjects in Part B (expansion) must have a diagnosis of any of the following: Histologically or cytologically confirmed advanced solid tumors of the following types:
    • Non-squamous NSCLC
    • TNBC
    • HNSCC
    • NPC
  • All subjects’ cancer must have progressed after treatment with standard/approved therapies or have no appropriate available therapies
  • Subjects must have measurable disease by RECIST 1.1
  • All subjects in Part A (dose escalation) must have adequate archival tumor sample
  • All subjects in Part B (dose expansion) must have a tumor lesion that can be biopsied at acceptable risk (in the judgment of the Investigator) and must agree to both a fresh biopsy during screening and a second biopsy following treatment
  • Subjects have an ECOG performance status of 0-1
Exclusion Criteria
  • Treatment with any PDL1 or PDL2-directed therapy within 4 weeks of the start of study drug
  • Prior treatment with an investigational anti-ICOS therapy
  • Treatment with nivolumab within 4 weeks of the start of study drug
  • Treatment with pembrolizumab within < 6 - 24 weeks prior to enrollment (cohort dependent)
  • Treatment with any other anticancer therapy within 2 weeks of the start of study drug (ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
  • A life-threatening (Grade 4) IRAE related to prior immunotherapy
  • Failure to recover from any IRAE from prior cancer therapy to Grade ≤ 1
  • Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2
  • Active known or suspected autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus or residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and non-steroidal anti-inflammatory drugs)
  • Receipt of an organ allograft
  • History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic or psychiatric) other than their primary malignancy, that in the opinion of the Investigator would pose a risk to patient safety or interfere with study evaluations, procedures, or completion
  • Treatment with antibiotics within 14 days prior to first dose of study drug

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT03752398

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Re: MC# 19-08