Trial Title:
A Study of MOv18 IgE in Folate Receptor Alpha-expressing Platinum Resistant Ovarian Cancer
NCT ID:
NCT06547840
Condition:
Advanced Ovarian Cancer
Platinum-resistant Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Conditions: Keywords:
Ovarian
Cancer
Resistant
IgE
Advanced
Platinum
Folate Receptor alpha
Antibody
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Bayesian logistic regression model with overdose control
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
MOv18 IgE
Description:
MOv18 IgE is an anti-FRα monoclonal antibody (mAb) of the IgE class
Arm group label:
Part 1 and Part 2
Summary:
EPS101-10-02 is a Phase Ib open label, multicentre clinical trial comprising of a Dose
Escalation phase (Part 1) followed by a Dose Expansion phase (Part 2) of MOv18 IgE in
patients with folate receptor alpha-expressing (5% or higher) platinum resistant ovarian
cancer
The dose escalation part of the study will primarily assess the safety and tolerability
of MOv18 IgE in ascending dose cohorts, until the determination of the maximum tolerated
dose (MTD) or maximum administered dose (MAD).
Part 2 (dose expansion) will further assess the safety, tolerability and anti-tumour
activity of MOv18 IgE.
Detailed description:
EPS101-10-02 is a two-part, Phase Ib, open-label, dose escalation and expansion trial in
patients with platinum resistant ovarian cancer whose disease has progressed after no
more than 4 lines of standard therapy.
In total, the trial will enrol approximately 45 patients. All enrolled patients will have
biopsy accessible, measurable disease with a confirmed FRα expression of 5% or higher.
MOv18 IgE will be administered to approximately 30 patients in Part 1 and up to a further
15 in Part 2.
Patients will receive treatment on Days 1, 8 and 15 of a 21-day cycle and may continue
treatment until radiological disease progression or unacceptable toxicity despite optimal
medical management or dose or schedule modification, or withdrawal of consent.
The starting dose of MOv18 IgE is 3 mg.
Patient screening will occur during the 28 days prior to the first administration of
MOv18 IgE. All patients will undergo PK, PD and safety assessments, as well as disease
response (tumour) assessments to determine the potential clinical benefit of MOv18 IgE.
In all instances, patients will be followed up for overall survival (OS) for a maximum of
270 days after their last dose of trial treatment, or until withdrawal of consent, lost
to follow-up, death, or the overall end of trial, whichever is earliest.
In Part 1, MOv18 IgE will be administered at increasing dose levels in different patient
cohorts of approximately 6 patients, until selection of the Part 2 dose. The dose of
MOv18 IgE administered in Part 1 will be escalated following a Bayesian logistic
regression model - Escalation with overdose control (BLRM-EWOC) trial design.
After determination of the Part 2 dose, up to 15 additional patients will be enrolled and
treated with MOv18 IgE at that dose to further assess anti-tumour activity of MOv18 IgE
and obtain additional information on its safety, PK and PD.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Female ≥18 years of age.
2. Written (signed and dated) informed consent.
3. Confirmed diagnosis by CT scan or MRI, of advanced epithelial ovarian, fallopian
tube cancer, or primary peritoneal cancer with histologically- high-grade serous or
endometrioid features or a predominantly serous/endometrioid component.
4. Tumour tissue expressing FRα (1+, 2+ or 3+ membrane staining on at least 5% of
tumour cells by immunohistochemistry using the BN3.2 antibody (Leica Biosystems).
5. Negative BAT assay prior to Cycle 1 Day 1. Note: this test may be performed in
duplicate at two different sites: (i) at the treatment centre (where possible), and
(ii) at a reference laboratory. Where results are discordant, (or in instances where
the treatment centre is not able to perform the assay), the reference laboratory
results will prevail.
6. Platinum-free interval since last line of platinum of less than 6 months (182 days).
7. Progressed following ≤4 prior regimens of anti-cancer therapy for ovarian cancer and
no other authorised therapy is considered appropriate in the opinion of the
investigator. Prior regimens can include carboplatin/paclitaxel, bevacizumab (if
clinically indicated), PARP inhibitors and FRα antibody-drug conjugates.
- Patients who received hyperthermic intraperitoneal chemotherapy (HIPEC) or
other IP therapies are eligible.
- Neoadjuvant and adjuvant therapy counts as a prior regimen.
8. Has measurable disease as defined by RECIST v1.1 on CT or MRI scan with at least one
lesion that is accessible by image-guided biopsy and which is not a target lesion.
1. Note: Qualification scans must be performed ≤28 days before Cycle 1 Day 1,
after discontinuation of the prior regimen.
2. Note: Lesions previously embolised, perfused, or irradiated without objective
evidence of progression before Cycle 1 Day 1 are not allowed to be considered
for response assessment.
9. No evidence of bowel obstruction.
10. ECOG Performance Status Score 0-1 prior to Cycle 1 Day 1.
11. Estimated life expectancy of >3 months, in the opinion of the Investigator.
12. Adequate haematological function, including all of the following:
1. ANC ≥1.5 × 109/L (>1,500/mm3). G-CSF or GM-CSF may not be used to achieve this
level.
2. Platelets ≥100 × 109/L (>100,000 per mm3).
3. Haemoglobin level ≥9 g/dL obtained within 14 days before Day 1. Packed red
blood cell transfusion is acceptable, if the patient has a stable result of ≥9
g/dL for at least 1 week post-transfusion. Erythropoietin should not be used to
achieve this level.
4. Adequate coagulation function at screening as determined by PT INR <1.5 and PTT
<1.5 × ULN.
5. Lymphocyte count >1500 cells/mm3.
13. Intact immune system as demonstrated by CD4 count >500 cells/mm3 and CD8 count >150
cells/mm3.
14. Adequate renal function as demonstrated by creatine or measured and calculated
creatinine clearance (estimated glomerular filtration rate [eGFR] can also be used
in place of creatinine or creatinine clearance [CrCl] - deduced using the
Cockcroft-Gault equation: creatinine clearance: (140-age [years]) × weight
(kg)/(serum creatinine [mg/dL] × 72) × 0.85 ≤1.5 × ULN, or ≥60 mL/min for a patient
with creatinine levels >1.5 × institutional ULN.
15. Adequate hepatic function:
1. Serum total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for a patient with
total bilirubin levels >1.5 × ULN.
2. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN or ≤5 × ULN for a patient with liver
metastases.
3. Albumin ≥3.0 g/dL.
16. Recovered from all chemotherapy-related toxicities to Grade ≤1 according to CTCAE
v5.0, excluding alopecia (any grade) and peripheral neuropathy (Grade ≤2).
17. No history of significant cardiac or pulmonary dysfunction, including but not
limited to interstitial pulmonary disease and chronic obstructive pulmonary disease.
18. No history of autoimmune disease.
19. Negative serum or urine pregnancy test.
20. Women of childbearing potential must have 2 negative pregnancy tests during
Screening, the second within 24 hours prior to the first administration of MOv18
IgE. This criterion does not apply to patients who have had a previous hysterectomy
or bilateral oophorectomy.
21. Female patients of child bearing potential must agree to practice true abstinence or
to use two forms of contraception, one of which must be highly effective. These
forms of contraception must be used from the time of signing consent, throughout the
treatment period, and for 6 months following the last dose of any study medication.
Oral or injectable contraceptive agents cannot be the sole method of contraception.
22. Willing and able to comply with all protocol-specified assessments and the trial
visit schedule.
23. Patient has been advised to take measures to avoid or minimise exposure of the skin
to UV light, including sunbathing and solarium use for the duration of the trial and
for 4 weeks following last administration of MOv18 IgE.
Exclusion Criteria:
1. Non-epithelial tumour origin of the ovary, the fallopian tube, or the peritoneum
(i.e., germ cell tumours).
2. Ongoing malignant ascites requiring drainage >500cc within 2 weeks prior to Day 1.
3. Anorexic and unable to eat.
4. Taking beta-blockers and unable to interrupt beta-blockade (which may counteract the
therapeutic effects of adrenaline), or tricyclic anti-depressants/MAOIs (which can
dangerously augment the effects of adrenaline). These agents should be discontinued
at least 4 half-lives before administration of the first dose of MOv18 IgE.
Treatment may be reintroduced 48 hours post dose administration.
5. History of laryngeal oedema, uncontrolled or high-risk asthma, or anaphylaxis.
Patients with a history of hypersensitivity to carboplatin, taxanes, or contrast
media may enter the trial at the Investigator's discretion.
6. History of parasitic infections, such as helminthiasis.
7. Baseline elevation in serum tryptase (indicating possible mastocytosis) or a
positive BAT. Tryptase normal range is 2-15 ng/mL.
8. Receiving systemic anti-cancer therapy, including immunostimulatory agents (e.g.,
cytokine-based modality, antigen-specific peptide immunotherapy, immune checkpoint
blockade, co-stimulatory agonists) within 28 days of Cycle 1 Day 1.
9. Administration of other simultaneous chemotherapy drugs, anti-cancer therapy or
anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial
treatment period (hormonal replacement therapy and denosumab is permitted).
10. Receiving radiation therapy within 14 days prior to Day 1. Local palliative
radiotherapy is permitted; however, if the radiotherapy is to a target lesion, that
lesion must be excluded from tumour response assessments.
11. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone (>10 mg), dexamethasone,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF agents)
within 14 days prior to Day 1, or anticipated requirement for systemic
immunosuppressive medications during the trial.
12. Administration of a live, attenuated vaccine within 28 days prior to Day 1 or
anticipation that such a live attenuated vaccine will be required during the trial
or within 5 months after the last dose of MOv18 IgE. Influenza vaccination should be
given during influenza season only. Patients must not receive live, attenuated
influenza vaccination. COVID vaccination is permitted as necessitated.
13. Previous allogeneic bone marrow transplant or previous solid organ transplantation.
14. Historical positive serology test for human immunodeficiency virus (HIV).
15. History of autoimmune disease, including but not limited to inflammatory bowel
disease, systemic lupus erythematosus, and autoimmune hepatitis.
16. History of interstitial lung disease or active pneumonitis.
17. Has a known hypersensitivity to a component of protocol therapy, MOv18 IgE or its
vehicle (sodium citrate, L-arginine, sucrose and polysorbate 20).
18. Positive serology for hepatitis B or C.
19. Uncontrolled concurrent illness including, but not limited to, ongoing or active
infection, or psychiatric illness.
20. Has a history within last 12 months or ongoing clinically significant cardiovascular
disease such as unstable angina, myocardial infarction, or acute coronary syndrome,
symptomatic or uncontrolled arrhythmia, left ventricular failure, congestive heart
failure, baseline ECG abnormalities that, in the Investigator's opinion, would be
likely to interfere with their participation in the study, or with the
interpretation of the results, including, but not limited to, QTc prolongation to
greater than 470 ms (as determined by the Fridericia formula), or any Class III or
IV cardiac disease as defined by the New York Heart Association Functional
Classification.
21. Concomitant use of drugs known to prolong QT/QTc interval (Appendix 1).
22. Has a fever ≥38oC within 3 days before the first dose of MOv18 IgE.
23. No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in-situ cervical cancer, surgically treated
Stage I or II cancer from which the patient is currently in complete remission (at
least to 5 years), or any other non-metastatic cancer controlled by surgery alone or
surgery plus radiotherapy from which the patient has been disease-free for 5 years.
24. Presence of CNS metastases (including spinal metastases) or CNS primary tumour,
e.g., glioblastoma.
25. Clinically significant illness or major surgery within 4 weeks before the
administration of MOv18 IgE.
26. Currently breastfeeding.
27. Any condition which could interfere with, or the treatment for which might interfere
with, the conduct of the trial, or which would, in the opinion of the Investigator,
unacceptably increase the patient's risk by participating in the trial
28. Patient is under legal custodianship.
29. First-degree relatives of the Investigator, trial staff or Sponsor employees.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Bristol Haematology and Oncology Centre
Address:
City:
Bristol
Zip:
BS2 8ED
Country:
United Kingdom
Status:
Not yet recruiting
Facility:
Name:
Edinburgh Cancer Research Centre
Address:
City:
Edinburgh
Zip:
EH4 2XR
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Leeds Teaching Hospitals NHS Trust
Address:
City:
Leeds
Zip:
LS9 7LP
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Cambridge University - Addenbrooke's Hospital
Address:
City:
London
Zip:
CB2 0QQ
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
University College London Hospital
Address:
City:
London
Zip:
NW1 2BU
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Guy's Hospital
Address:
City:
London
Zip:
SE1 3SS
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
University Hospital Southampton NHS Foundation Trust
Address:
City:
Southampton
Zip:
SO16 6HU
Country:
United Kingdom
Status:
Not yet recruiting
Start date:
September 3, 2024
Completion date:
March 2027
Lead sponsor:
Agency:
Epsilogen Ltd
Agency class:
Industry
Source:
Epsilogen Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06547840
