A Study of XmAb®22841 Monotherapy & in Combination w / Pembrolizumab in Subjects w / Selected Advanced Solid Tumors
Trial Status: Active
This is a Phase 1, multiple dose, ascending-dose escalation study and expansion study designed to define a maximum tolerated dose and / or recommended dose of XmAb22841 monotherapy and in combination with pembrolizumab; to assess safety, tolerability, pharmacokinetics, immunogenicity, and anti-tumor activity of XmAb22841 monotherapy and in combination with pembrolizumab in subjects with select advanced solid tumors.
- All subjects' cancer must have progressed after treatment with all available therapies that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment.
- All subjects must have adequate archival tumor, or give consent to a fresh tumor biopsy.
- Subjects have an ECOG performance status of 0-1.
- Subjects in monotherapy and combination therapy cohorts must have histologically or cytologically confirmed advanced or metastatic 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
- Microsatellite instability-high or mismatch repair deficient tumors
- Small cell lung carcinoma or NSCLC
- Gastric or gastroesophageal junction adenocarcinoma
- Prostate adenocarcinoma
- Epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer
- Intrahepatic cholangiocarcinoma
- Subjects in the combination cohorts in Part A with XmAb22841 and pembrolizumab may have an advanced solid tumor that either:
- has progressed after treatment with all available therapies that are known to confer clinical benefit, or is intolerant or has refused standard treatment (as for the XmAb22841 monotherapy cohorts), or
- is of a tumor type for which pembrolizumab is an approved indication and has not previously been treated with an agent targeting PD1 or PDL1.
- 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 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, OX 40, 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.
- 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; 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.
- Treatment with antibiotics within 14 days prior to first dose of study drug.
- Participants with known HIV.
- 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.
UCLA / Jonsson Comprehensive Cancer Center
Contact: Louis Slonlker
University of California San Diego
Emory University Hospital / Winship Cancer Institute
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Wayne State University / Karmanos Cancer Institute
Siteman Cancer Center at Washington University
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
University of Pennsylvania / Abramson Cancer Center
University of Pittsburgh Cancer Institute (UPCI)
M D Anderson Cancer Center
Contact: Shubham Pant
Salt Lake City
Huntsman Cancer Institute / University of Utah
Trial Phase Phase I
Trial Type Treatment
- Primary ID XmAb22841-01
- Secondary IDs NCI-2019-02498, DUET-4
- Clinicaltrials.gov ID NCT03849469