MC# 19-07 - A Phase I Multiple-Dose Study to Evaluate the Safety and Tolerability of XmAb®22841 Monotherapy and in Combination with Pembrolizumab in Subjects with Selected Advanced Solid Tumors

  • Agent(s): XmAb22841
  • Disease Type(s): Breast- Triple Negative, Renal, Pancreatic, Melanoma, Lung-SCLC, Lung-NSCLC, Hepatocellular, Head and Neck, Gastric, Endometrial, Colorectal, Cervical, Nasopharyngeal, Bladder
  • Phase(s): I
  • Drug Classification(s): Bispecific Antibodies
  • Molecular Target(s): CTLA4, LAG3

Mechanism of Action

XmAb22841 is an anti- CTLA4/ LAG3 bispecific monoclonal antibody. It binds to both CTLA4 and LAG3 expressed on certain cells, including tumor-infiltrating lymphocytes (TILs). It will be combined with anti-PD1 antibodies to achieve highly active triple checkpoint blockade.

Purpose

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

  • How much of XmAb22841 can be given with an acceptable level of side effects when given alone or in combination with Pembrolizumab
  • The effects of XmAb22841 (good and bad) when given alone or in combination with Pembrolizumab
  • How fast XmAb22841 is removed from the blood when given alone or in combination with Pembrolizumab
  • How you immune system reacts to XmAb22841 when given alone or in combination with Pembrolizumab
  • If research tests can be used in the future to predict who will benefit from XmAb22841
Inclusion Criteria
  • Subjects are adults (age ≥ 18 years) on day of signing informed consent
  • Subjects must have measurable disease by RECIST 1.1
  • All subjects (dose escalation) must have adequate archival tumor sample
  • Subjects have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Subjects in Part A monotherapy and combination cohorts must have histologically or cytologically confirmed advanced or metastatic solid tumor that has progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment, including the following tumor types:
  • Melanoma (excluding uveal melanoma)
    • Cervical carcinoma
    • Pancreatic carcinoma
    • Breast carcinoma that is estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) negative (triple negative breast cancer [TNBC])
    • Hepatocellular carcinoma
    • Urothelial carcinoma
    • Squamous cell carcinoma of the head and neck
    • Nasopharyngeal carcinoma
    • Renal cell carcinoma (clear cell predominant type)
    • Microsatellite instability-high or mismatch repair deficient colorectal carcinoma or endometrial carcinoma
    • Small cell or non-small cell lung carcinoma
    • Gastric or gastroesophageal junction adenocarcinoma
    • Prostate adenocarcinoma
    • Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
    • Intrahepatic cholangiocarcinoma
  • Subjects in the Part A combination cohorts must have histologically or cytologically confirmed advanced solid tumors for which pembrolizumab is an approved indication and that has not previously been treated with an agent targeting PD1 or PDL1
Exclusion Criteria
  • Prior treatment with an investigational anti-LAG3 therapy
  • Treatment with any CTLA4 antibody within 16 weeks of the start of study drug for Cohorts 1M, 2M, 3M, 1P, and 2P; within 8 weeks of the start of study drug for Cohorts 4M, 5M, 3P, and 4P; and within 3 weeks for Cohorts 6M, 7M, 5P, and 6P
  • Systemic antineoplastic therapy, unconjugated antibody therapy within 4 weeks of the first dose of study treatment; or radiotherapy within 2 weeks of the first dose of study treatment; or small molecule kinase inhibitors within 6 elimination half-lives of the first dose of study treatment
  • Have received prior therapy with an anti-PD1, anti-PDL1, or anti PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA4, OX40, CD137) AND were permanently discontinued from that treatment due to an IRAE
  • Failure to recover from any IRAE from prior cancer therapy to Grade ≤ 1 (participants with Grade ≤ 2 neuropathy or endocrinopathies controlled by hormone replacement are eligible)
  • Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2
  • Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable
  • Active known or suspected autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus; 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 nonsteroidal anti-inflammatory drugs [NSAIDS])
  • Participants with known chronic hepatitis B virus (HBV) infection treated for less than 3 months prior to study enrollment and/or with a detectable HBV viral load; or hepatitis C virus (HCV) infection that has been treated for less than 4 weeks prior to study enrollment and/or with a detectable HCV viral load; or active HBV/HCV coinfection
  • Have had an allogenic tissue/solid organ transplant
  • Treatment with antibiotics within 14 days prior to first dose of study drug
  • Participants with known HIV infection

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT03849469

Contact Us About This Trial

Reach out to us by sharing your info in the form below or give us a call at 972-566-3000.

Re: MC# 19-07