Clinical Trial 23993

• Overview

  Study Title:

  A Phase 1a/1b, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of IMGS-001 in Patients with Relapsed or Refractory Advanced Solid Tumors

  Summary:

  The purpose of this Phase 1a/1b clinical trial is to test the safety of an investigational drug called IMGS-001 and to determine how well it can work in treating patients with advanced solid tumors that have come back or are not improving after receiving other drugs that are commonly used for their cancer. Phase 1a (Part 1) will test the safety of five different doses of IMGS-001 to use in further studies. Patients with cancer that have advanced or spread to other parts of the body following treatment with other available therapies will be treated in Part 1. Phase 1b (Part 2) will test two doses of IMGS-001 identified in Part 1 to further determine the safety and potential effectiveness in select cancer types.

  Objective:

  Phase 1a (Part 1 Dose-escalation) Primary Objectives - To assess the safety and tolerability of IMGS-001 by dose-limiting toxicities (DLTs) and AEs Secondary Objectives - To determine the maximum tolerable dose (MTD) of IMGS-001 - To assess the PK profile of IMGS-001 - To assess the potential immunogenicity of IMGS-001 by development of anti-drug antibodies (ADAs) - To evaluate preliminary anti-tumor activity of IMGS-001 by ORR via immune Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1, duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS) - Phase 1b (Part 2 Dose-expansion) Primary Objectives: - To define a recommended Phase 2 dose (RP2D) of IMGS-001 for specified disease-specific cohorts as a pharmacologically optimal dose (POD) after pooling and evaluating all available PK, PD, target engagement, efficacy, safety, and tolerability data from Part 1 and Part 2 Secondary Objectives: - To evaluate anti-tumor activity of IMGS-001 by ORR, DOR, DCR, CBR, PFS (by iRECIST and RECIST v1.1) and OS - To assess the safety and tolerability of IMGS-001 by frequency and severity of AEs - To assess the PK profile using population-based sampling of IMGS-001 - To assess the potential immunogenicity of IMGS-001 by development of ADAs

• Treatments

  Therapies:

  Dual-specific immunoglobulin G1 (IgG1) monoclonal antibody

  Medications:

  IMGS-001 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Part 1 Dose-escalation: Patients must have histologically confirmed locally advanced, or metastatic solid tumors who have progressed after receiving appropriate lines of standard therapy known to potentially confer clinical benefit.
  • Part 2 Dose-expansion: Patients must have histologically confirmed locally advanced, or metastatic cancer in one of the following pre-specified tumor types and meet tumor-specific criteria.
  • Prostate cancer patients enrolled in Part 1 dose escalation must continue ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analog or have undergone a bilateral orchiectomy (surgical or medical castration) and must have a serum testosterone ≤1.73 nmol/L (50 ng/dL) at screening.
  • Colorectal patients participating in Part 2 (Phase 1b) must have confirmed PD-L1 positive expression (CPS ≥ 5 or TPS ≥ 5%) using local laboratory results based on prior results obtained within 6 months of baseline, expression testing done on archived tissue within 6 calendar months of baseline, or fresh biopsy.
  • Male or female ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
  • Life expectancy > 3 months.
  • At least one measurable lesion as defined by RECIST 1.1.
  • Patients must have a non-target lesion that can be biopsied. If a patient only has one target lesion (and no non-target lesions) the target lesion used for biopsy must be ≥ 2 cm in longest diameter. Eligible subjects for biopsy must be clinically appropriate, including specimens attainable and on appropriate subjects without presenting high risk of major complications. Subjects who are unable to undergo a biopsy at screening must submit archival tumor tissue retrieved within the last 6 months.
  • Additional criteria will apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Receipt of any investigational or conventional anti-cancer drug/therapy within 21 days of Cycle 1 Day 1.
  • Current or prior use of immunosuppressive medication within 14 days of Cycle 1 Day 1. Inhaled and intranasal corticosteroids are allowed.
  • Current or prior use of interleukin-2, interferon, or other immunotherapy medication within 28 days of Cycle 1 Day 1.
  • Live vaccine within 28 days prior to Cycle 1 Day 1.
  • Any toxicity from prior standard therapy that has not resolved to ≤ Grade 1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 at the time of consent. Alopecia is an exception. Any patients with irreversible Grade 1 or Grade 2 toxicities that are considered stable may be enrolled after discussion with the Medical Monitor.
  • Prior anti-PD-1 or anti-PD-L1-related Grade 3 or Grade 4 toxicity resulting in treatment discontinuation of the drug.
  • Secondary malignancy other than the target malignancy to be investigated in this trial within the last 2 years.
  • History of myocardial infarction, ischemic heart disease, symptomatic congestive heart failure (New York Heart Association (NYHA) Class III IV), or significant cardiac arrhythmias within 3 months of study enrollment.
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) or pulmonary embolism within 3 months of study enrollment.
  • History of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis, bowel perforation, or other known risk factors for bowel perforation.
  • Active, uncontrolled, or prior documented autoimmune disorders including but not limited to inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, systemic sclerosis (scleroderma), Systemic Lupus Erythematosus, or autoimmune vasculitis (e.g., Wegener's Granulomatosis). Alopecia, vitiligo, celiac disease controlled by diet, and chronic skin conditions not requiring systemic therapy/immunosuppressive treatment is permitted.
  • Uncontrolled intercurrent illness, including active infection requiring systemic therapy, uncontrolled hypertension (> 150/90mm Hg despite optimal medical management), uncontrolled asthma, psychiatric illness/social situations, substance abuse, or other underlying medical conditions that would limit compliance with study requirements, obscure the interpretation of AEs, substantially increase the risk of developing AEs, or make the administration of study treatment hazardous.
  • Active human immunodeficiency virus (HIV) infection (Exception: patients with well-controlled HIV [e.g., CD4 ≥ 350 cells/uL and undetectable viral load] who have been on an effective [drug, dosage, and schedule associated with reduction and control of the viral load] antiretroviral therapy [ART] for ≥ 4 weeks are eligible). Patients with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last 12 months are not eligible.
  • Active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with a history of HCV infection must have completed curative antiviral treatment and must have a viral load below the limit of quantification. A patient who is HCV antibody (Ab) positive but HCV RNA negative due to prior treatment or natural resolution is eligible. History of solid organ transplantation.
  • Additional criteria will apply.

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