Patient case: 58-year-old female with endometrial cancer; genetic feature: PIK3R1

Clinical trial: A Study of XmAb®23104 in Subjects With Selected Advanced Solid Tumors (DUET-3)

Summary: This is a Phase 1, multiple dose, ascending dose escalation study to define a MTD/RD and regimen of XmAb23104, to describe safety and tolerability, to assess PK and immunogenicity, and to preliminarily assess anti-tumor activity of XmAb23104 in subjects with selected advanced solid tumors.


Eligibility: Inclusion Criteria:
  1. Subjects in Part A (dose escalation) must have a diagnosis of any of the following:
  1. Histologically or cytologically confirmed advanced solid tumors, including the following:
  2. Melanoma (excluding uveal melanoma)
  3. Cervical carcinoma
  4. Pancreatic carcinoma
  5. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2 negative (TNBC)
  6. Hepatocellular carcinoma
  7. Urothelial carcinoma
  8. Squamous cell carcinoma of the head and neck (HNSCC)
  9. Nasopharyngeal carcinoma (NPC)
  10. Renal cell carcinoma
  11. Colorectal carcinoma
  12. Endometrial carcinoma
  13. NSCLC
  14. Small cell lung cancer
  15. Gastric or gastroesophageal junction adenocarcinoma
  2. 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:
  1. Non-squamous NSCLC
  2. TNBC
  3. HNSCC
  4. NPC
  3. All subjects' cancer must have progressed after treatment with standard/approved therapies or have no appropriate available therapies.
  4. Subjects must have measurable disease by RECIST 1.1.
  5. 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.
  6. Subjects have an ECOG performance status of 0-1.
  Exclusion Criteria:
  1. Treatment with any PDL1 or PDL2-directed therapy within 4 weeks of the start of study drug
  2. Prior treatment with an investigational anti-ICOS therapy
  3. Treatment with nivolumab within 4 weeks of the start of study drug
  4. Treatment with pembrolizumab within < 6 - 24 weeks prior to enrollment (cohort dependent)
  5. Treatment with any other anticancer therapy within 2 weeks of the start of study drug (ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
  6. A life-threatening (Grade 4) IRAE related to prior immunotherapy
  7. Failure to recover from any IRAE from prior cancer therapy to Grade ≤ 1
  8. Failure to recover from any other toxicity (other than immune-related toxicity) related to previous anticancer treatment to Grade ≤ 2
  9. 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)
  10. Receipt of an organ allograft
  11. 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
  12. Treatment with antibiotics within 14 days prior to first dose of study drug

Relevance to patient case: not relevant