Ovarian Cancer
Conditions
Keywords
anti-CD47 therapy, platinum resistance, macrophage mediated phagocytosis, checkpoint inhibitors
Brief summary
Immunotherapy with immune checkpoint inhibitors, including pembrolizumab, have emerged as a promising option in several solid cancers with durable effect and low toxicity profile. However, the benefit is limited to smaller subset of solid tumors. This trial involves the enhancement of current immune checkpoint-based immunotherapy with ALX148, an agent that inhibits CD47 (a trans-membrane protein that is highly expressed on the surface of many solid tumors as compared to normal cells).
Detailed description
All patients on this study will receive Pegylated Liposomal Doxorubicin (PLD) as standard of care combined with pembrolizumab and ALX148 iv every 21 days. Treatment of 45 mg/kg Q3W ALX148 in combination with pembrolizumab + chemotherapy will continue until disease progression or unacceptable grade 3/4 toxicities. For patients with a complete response to therapy, maintenance therapy with pembrolizumab and ALX148 will be continued for 12 months. Patients will have up to 4 weeks of screening, and will be treated until disease progression, patient withdraws consent, unacceptable toxicity occurs, complete response or the study is terminated. Patients may continue treatment after radiographic progression if, in the judgment of the treating investigator the patient is deriving clinical benefit from study treatment by demonstrating an absence of clinical symptoms or signs indicating clinically significant disease progression; no decline in performance status; absence of rapid disease progression or threat to vital organs or critical anatomical sites. A follow-up visit will occur within between 28 days and 35 days after the last treatment.
Interventions
DRUGPembrolizumab
A type of immunotherapy that stimulates the body's immune system to fight cancer cells by targeting and blocking PD-1 proteins on the surface of certain immune T-cells, thus triggering the T-cells to find and kill cancer cells.
DRUGALX148
A fusion protein comprised of a high affinity CD47 blocker linked to an inactive immunoglobulin Fc region, enhancing innate and adaptive immune responses against cancer.
DRUGDoxorubicin
An anthracycline that slows/stops the growth of cancer cells by blocking an enzyme called topo isomerase 2, used as second line non-platinum chemotherapy in patients with platinum-resistant ovarian cancer.
Sponsors
Alexander B Olawaiye, MD
ALX Oncology
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants must have recurrent epithelial ovarian cancer. 2. Platinum-resistant disease: Patients who recur within \< 6 months of prior platinum-based therapy excluding those with primary platinum refractory disease (see
Exclusion criteria
). 3. Following histology types are acceptable: high grade serous or high grade endometrioid, clear cells, high grade translational cell, poorly differentiated or undifferentiated carcinomas, mixed histology (including one of above histology). 4. 0-3 prior lines in platinum-resistant setting. 5. Known BRCA status or willing to be tested. 6. Up to 5 prior lines of therapy are allowed. 7. Participants must have measurable disease based on RECIST 1.1 with at least one target lesion. 8. Participants must have an ECOG performance status of 0-1. 9. Participants must be female, Age \>18 years. Because no dosing or AE data are currently available on the use of pembrolizumab in combination with ALX148 in participants ≤18 years of age, children are excluded from this study. 10. Participants must have normal organ and marrow function as defined below within 14 days of enrollment unless otherwise indicated. 11. Participants must have the ability to understand and the willingness to sign a written informed consent document. 12. Negative serum or urine pregnancy test at screening for women of childbearing potential. 13. Willing to use highly effective contraception throughout the study and for at least 4 months after last treatment administration if childbearing potential exists. 14. Availability of an archival FFPE tumor tissue block from primary diagnosis specimen, metastatic, or recurrent site. If an FFPE tissue block cannot be provided then 15 unstained slides (10 microns, 10 slides minimum) will be acceptable. Please refer to the laboratory manual for complete details.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 3 years (cohort) | The proportion of patients having either a complete response (CR) or partial response (PR), per RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. For non-target lesions, CR is the disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 5 years | The number of months from the date of study enrollment until date of death ( from any cause) or last known date of follow up if otherwise lost to follow up. |
| Progression-free survival (PFS) | Up to 5 years | The number of months from the date of study enrollment to the date of an event of disease progression (per RECIST 1.1) or to the date of death from any cause. Progressive Disease (PD) as defined by RECIST v1.1 for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. |
| Objective response rate Immune-related Response Criteria (iRECIST) | Up to 3 years (cohort) | The proportion of patients with complete or partial response per iRECIST. irCR (Complete Response):Disappearance of non-nodal lesions. All pathologic lymph nodes \<10 mm (2 consecutive measures ≥4 weeks apart); irPR (Partial Response):≥30% decrease from baseline (2 consecutive measures ≥4 weeks apart); All pathologic lymph nodes \<10 mm (Non-Target Lesions: Any other than disappearance of all non-nodal lesions and reduction of pathologic lymph nodes \<10 mm). Baseline tumor burden: sum of single diameters (short axis for nodal lesions, longest diameter for other lesions) for target lesions. In subsequent scans, the diameters of new measurable lesions are added to the tumor burden. Re-treatment: ≤5 target lesions (=/≠ original lesions) are selected and a new baseline tumor burden will be established. |
| Duration of response (DOR) | Up to 3 years (cohort); at 12 weeks (patient) | The number of months from the date of study enrollment to the date of disease progression or death in those participants who achieve complete or partial response per RECISIT 1.1. Complete Response (CR): Disappearance of all target lesions. For non-target lesions, CR is the disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change not a single lesion increase. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAlexander B Olawaiye, MD
UPMC Hillman Cancer Center
Outcome results
None listed