| Eligibility |
Inclusion Criteria:
1. Have signed an Institutional Review Board/Independent Ethics Committee-approved
informed consent form prior to any study-specific evaluation.
2. Histologically diagnosed epithelial ovarian, fallopian tube or primary peritoneal
cancer.
3. Radiological or histological confirmation of relapse disease = 6 month after last
chemotherapy
4. Known BRCAwt
5. Have completed at least one line of platinum-containing chemotherapy (maximum three
previous lines of therapy are permitted). Earlier PARPi treatment permitted
6. Must have measurable or evaluable disease according to RESIST 1.1.
7. Baseline biopsy: Tissue biopsy for submission to central laboratory prior to study
treatment should be from a newly obtained metastatic biopsy, if there is a lesion
suitable for biopsy. If a metastatic biopsy is not feasible, or patient is unwilling
to provide new biopsy, archival tissue samples should be submitted. Archival tissue
sample from metastatic site is preferred; however, archival tissue sample of primary
tumor is acceptable.
8. Must consent to undergo mandatory tumor biopsy of at least one metastatic site at
baseline and at day 84 ( 7). Biopsy at day 84 ( 7) is only applicable if surgery is
not performed. -
Exclusion Criteria:
1. Previous immunotherapy (for example anti-PD-1/L1).
2. Other malignancy unless curatively treated with no evidence of disease for = 3years,
except adequately treated non-melanoma skin cancer, curatively treated in situ cancer
of the cervix, ductal carcinoma in situ (DCIS) and stage 1 grade 1 endometrial
carcinoma.
3. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as
judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic
arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte
disturbances, etc.), or subjects with congenital long QT syndrome.
4. Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features
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5. Subjects with symptomatic uncontrolled brain metastases. A scan to confirm the absence
of brain metastases is not required. Subjects with spinal cord compression unless
considered to have received definitive treatment for this and evidence of clinically
stable disease for 28 days.
6. Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
days of randomization. Subjects who have received acute, low-dose, systemic
immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) or
physiologic replacement doses (i.e. prednisone 5 - 7.5 mg/day) for adrenal
insufficiency may be enrolled in the study. Inhaled or topical steroids, and adrenal
replacement steroid doses = 10 mg daily prednisone equivalent, are permitted in the
absence of active autoimmune disease.
7. Prior radiation therapy.
8. Planned concomitant therapy with any other anticancer therapy
9. Conditions requiring ongoing therapy with antibiotics
10. History of any arterial thromboembolic event within 3 months prior to first dose of
APX005M
11. Active coagulopathy
12. Previous allogeneic bone marrow transplant or double umbilical cord blood
transplantation
13. History of organ transplant
14. Major surgery or significant traumatic injury within 4 weeks prior to first dose of
study drugs
15. Pregnant or breastfeeding women.
16. Subjects with a known hypersensitivity to any of the excipients of the product.
17. Any unresolved toxicity NCI CTCAE Grade = 2 from previous anticancer therapy, except
alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
1. Subjects with Grade = 2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Lead Principal Investigator (PI) of the respective
collaborative group
2. Subjects with irreversible toxicity not reasonably expected to be exacerbated by
treatment with study drugs may be included only after consultation with the Lead
PI of the respective collaborative group.
18. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
criterion:
1. Subjects with vitiligo or alopecia
2. Subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on
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3. Any chronic skin condition that does not require systemic therapy
4. Subjects without active disease in the last 5 years may be included, but only
after consultation with the Lead PI of the respective collaborative group.
5. Subjects with celiac disease controlled by diet alone
19. Subjects considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled symptomatic congestive heart failure,
uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, recent
(within 3 months), uncontrolled major seizure disorder, serious chronic
gastrointestinal conditions associated with diarrhea, interstitial lung disease or any
psychiatric disorder/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the ability of
the Subject to give written informed consent.
20. Immunocompromised subjects, e.g. subjects who are known to be serologically positive
for human immunodeficiency virus (HIV).
21. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg)), hepatitis
C.
Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B
core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA.
22. Receipt of live attenuated vaccine within 30 days prior to the first dose of
Investigational Product (IP). Note: Subjects, if enrolled, should not receive live
vaccine whilst receiving IP and up to 30 days after the last dose of IP. COVID-19
vaccination must be performed minimum 7 days prior to first dose of APX005M. -
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