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
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Agent(s): XmAb23104
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Disease Type(s): Colorectal, Melanoma, Sarcoma, Renal, Lung-NSCLC, Squamous Cell Carcinoma of Head and Neck
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Phase(s): I
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Drug Classification(s): Bispecific Antibodies
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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
- Sarcoma
- 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
- Melanoma
- HNSCC, including NPC
- CRC
- UPS, including other select high-grade STS, such as MFS
- RCC, clear cell histology (ccRCC)
- 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
