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 monotherapy and combination therapy with ipilimumab in subjects with selected advanced solid tumors.
Recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| XmAb®23104 | XmAb®23104 Combination Therapy with Ipilimumab | |
| Yervoy® (ipilimumab) | XmAb®23104 Combination Therapy with Ipilimumab |
| Name | Type | Description | Interventions |
|---|---|---|---|
| XmAb®23104 Monotherapy | Experimental | XmAb®23104 administered by IV dosing on Days 1 and 15 of each 28-day cycle x 2 cycles |
|
| XmAb®23104 Combination Therapy with Ipilimumab | Experimental | XmAb®23104 administered by IV on Days 1 and 15 of each 28-day cycle x 2 cycles + Yervoy® (ipilimumab) |
|
Inclusion Criteria:
1. 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:
1. Melanoma (excluding uveal melanoma)
2. Cervical carcinoma
3. Pancreatic carcinoma
4. Breast carcinoma that is estrogen receptor, progesterone receptor, and Her2
negative
5. Hepatocellular carcinoma
6. Urothelial carcinoma
7. Squamous cell carcinoma of the head and neck
8. Nasopharyngeal carcinoma
9. Renal cell carcinoma
10. Colorectal carcinoma
11. Endometrial carcinoma
12. NSCLC
13. Small cell lung cancer
14. Gastric or gastroesophageal junction adenocarcinoma
15. Sarcoma
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. Melanoma
3. HNSCC, including NPC
4. CRC
5. UPS, including other select high grade STS, such as MFS
Prior to enrolling into Part B (expansion), subjects should have received
disease-specific standard therapy as indicated for:
1. Non-squamous NSCLC
2. Melanoma
3. HNSCC, including NPC
4. CRC
5. UPS, including other select high-grade STS such as MFS
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 must have adequate archival tumor sample (slides or archival FFPE
block[s] containing tumor.
6. 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.
7. Subjects have an ECOG performance status of 0-1.
Exclusion Criteria:
1. Currently receiving other anticancer therapies
2. Prior treatment with an investigational anti-ICOS therapy
3. Treatment with any PDL1 or PDL2-directed therapy within 4 weeks of the start of study
drug
4. Treatment with nivolumab within 4 weeks of the start of study drug
5. Treatment with pembrolizumab within 24 weeks of start of study drug for Cohorts 1A -
10A
6. Treatment with any other anticancer therapy within 2 weeks of the start of study drug
(ie, other immunotherapy, chemotherapy, radiation therapy, etc.)
7. A life-threatening (Grade 4) irAE related to prior immunotherapy
8. Failure to recover from any irAE from prior cancer therapy to Grade ≤ 1, except for
endocrinopathies that are on stable hormone replacement doses
9. Failure to recover from any other toxicity (other than immune-related toxicity)
related to previous anticancer treatment to Grade ≤ 2
10. Known active central nervous system involvement by malignant disease. Subjects with
previously treated brain metastases may participate provided they are radiologically
stable, ie, are without evidence of progression for at least 4 weeks by repeat imaging
and are clinically stable and without requirement of steroid treatment for at least 14
days prior to first dose of study treatment.
11. Active known or suspected autoimmune disease
12. Receipt of an organ allograft
13. 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
14. Treatment with antibiotics within 14 days prior to first dose of study drug
15. Receipt of a live-virus vaccine within 30 days prior to first dose of study drug
(seasonal flu vaccines that do not contain live virus are permitted).
16. Treatment with ipilimumab within 4 weeks of the start of study drug
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Treatment-related adverse events as assessed by CTCAE v4.03 |
| Time Frame: | 56 Days |
| Safety Issue: | |
| Description: | Safety and tolerability |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Xencor, Inc. |
May 14, 2021
