Angiosarcoma
Conditions
Brief summary
This Phase 2, open-label study is designed to examine the efficacy and safety of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 in patients with recurrent, inoperable or metastatic Angiosarcoma (AS).
Detailed description
This Phase 2, open-label study is designed to examine the efficacy and safety of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 in patients with recurrent, inoperable or metastatic AS. Three cohorts will be enrolled into 2 Parts of the study as follows: Part 1 * Cohort 1: Qualifying patients that are checkpoint inhibitor naïve will be enrolled into single-agent AGEN2034 * Cohort 2: Qualifying patients that are inhibitor (PD-1/L1) resistant will be enrolled into combination AGEN2034 + AGEN1884 Part 2 • Cohort 3: Qualifying patients that are checkpoint inhibitor naïve will be enrolled into combination AGEN2034 + AGEN1884. Part 2 will begin enrollment after enrollment in Part 1 is completed The study will be conducted in 2 parts: In Part 1, checkpoint inhibitor naïve patients will be treated with single-agent AGEN2034 (Cohort 1) and patients resistant to PD-1/PD-L1 (defined as prior progression on PD 1/PD-L1 treatment) will be treated with combination of AGEN2034+AGEN1884 (Cohort 2). Patients from Cohort 1 who experience PD may be considered (as PD-1 resistant) for transition to Cohort 2. In Part 2, the study will enroll checkpoint inhibitor naïve patients for treatment with combination AGEN2034+AGEN1884 (Cohort 3). Part 2 will begin enrollment after enrollment in Part 1 is completed. All patients will receive study treatment for up to 2 years until confirmed disease progression, unacceptable toxicity, or until the patient wishes to withdraw consent for any reason. Patients will be followed for safety at 30 and 90 days, and for survival every 2 months for at least 12 months from their last dose of study treatment. Each treatment cycle will be 6 weeks. An IRC will be established to adjudicate tumor response based on imaging studies, photography, and clinical response. The primary endpoints will be based on the IRC assessment of response per RECIST v1.1.
Sponsors
Agenus Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for this study, patients must meet the following inclusion criteria: 1. Histologically confirmed AS not amenable to curative intent surgery 2. Prior treatment history for AS 1. Cohort 1 and Cohort 3 * Patients who previously received and progressed after at least 1 prior therapy for AS. * Checkpoint inhibitor (PD-1/PD-L1/CTLA-4) naïve 2. Cohort 2 * Patients who previously received and progressed on or after at least 1 prior therapy for AS * Prior treatment must include PD-1 or PD-L1 inhibitor such as nivolumab, pembrolizumab, atezolizumab, durvalumab, AGEN2034, or other, given either as the most recent treatment or earlier. Note: Confirmation of PD is required after treatment with prior checkpoint inhibitors * CTLA-4 inhibitor naïve 3. ≥ 18 years of age. 4. At least one lesion measurable, either radiologically (computed tomography \[CT\], magnetic resonance imaging \[MRI\]) and/or using color photography with a ruler, as per RECIST v1.1 5. Have a life expectancy of ≥ 3 months and an Eastern Cooperative Oncology Group Performance Status of 0 to 1 6. Resolution of all acute AEs resulting from prior cancer therapies to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 Grade ≤ 1 7. Have adequate organ function as indicated by the following laboratory values: 1. Adequate hematological function defined by absolute neutrophil count \> 1.5 × 10\^9/L, platelet count \> 75 × 10\^9/L, and hemoglobin \> 8 g/dL (without transfusions, within 1 week of first dose) 2. Adequate hepatic function based by a total bilirubin level ≤ × 1.5 the upper limit of normal (ULN), aspartate aminotransferase level ≤ 2.5 × ULN, alanine aminotransferase level ≤ 2.5 × ULN, alkaline phosphatase ≤ 2.5 × ULN, and albumin ≥ 3.0 mg/dL 3. Adequate renal function defined as creatinine ≤ 1.5 × ULN OR measured or calculated creatinine clearance ≥ 40 mL/minute per Institutional standard. Assessment methods should be recorded 4. Adequate coagulation defined by international normalized ratio or prothrombin time ≤ 1.5 × ULN (unless the patient is receiving anticoagulant therapy); and activated partial thromboplastin time ≤ 1.5 × ULN (unless the patient is receiving anticoagulant therapy) 8. Willing to undergo mandatory fresh tumor biopsy, from a site not previously irradiated (unless progressed after radiation treatment) Note: Tissue from core, or punch excisional biopsy, or from resection is required 9. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test at Screening (within 72 hours prior to first dose of study medication) Note: Non-childbearing potential is defined as 1 of the following: 1. ≥ 45 years of age and has not had menses for \> 1 year 2. Amenorrheic for \> 2 years without a hysterectomy and/or oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon pre-study (Screening) evaluation 3. Status is post hysterectomy, oophorectomy, or tubal ligation 10. WCBP must be willing to use highly effective contraception throughout the study, starting with the Screening Visit through 90 days after the last dose of study treatment 11. Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the Screening Visit through 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner Note: Abstinence is acceptable if this is the established and preferred contraception method for the patient 12. Willingness and ability to consent to participate in study and comply with all study procedures
Exclusion criteria
To be eligible for this study, patients must not have any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 | 48 months | To evaluate the response rate of single-agent AGEN2034 and combination AGEN2034 + AGEN1884 per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in patients with recurrent angiosarcoma |
Outcome results
None listed