Trial Title:
A Study of QL1706 (an Anti-PD-1/CTLA-4 Combined Antibody) Combined With Albumin-bound Paclitaxel and Bevacizumab in the Treatment of Platinum-resistant Recurrent Ovarian Cancer
NCT ID:
NCT06509971
Condition:
Platinum-resistant Recurrent Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Recurrence
Paclitaxel
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
QL1706
Description:
The Order of Drug Administration was: QL1706→ bevacizumab → albumin-binding paclitaxel,
and each drug was administered at least 30 minutes apart.
QL1706: 5 mg/kg Q3W. The infusion time was 30 minutes + 5 minutes. No dose adjustment was
allowed for QL1706 during treatment, but delayed administration was allowed, with a delay
of no more than 4 weeks from the previous dose.
Albumin-binding paclitaxel: 260 mg/m 2 Q3W, IV, for 30 min + 5 min. During treatment,
albumin-binding paclitaxel allows for dose adjustments.
Bevacizumab: 15 mg/kg Q3 W, iv. The first infusion should last 90 minutes. If the first
infusion was well tolerated, the second infusion could be shortened to 60 minutes. If the
patient is also well-tolerated for a 60-minute infusion, then all subsequent infusions
can be completed in 30 minutes, no dose adjustment is allowed for bevacizumab.
Arm group label:
Experimental Arm
Other name:
bevacizumab
Other name:
albumin-binding paclitaxel
Summary:
- Major objectives To evaluate the efficacy of QL1706 combined with albumin-binding
paclitaxel and bevacizumab in the treatment of platinum-resistant recurrent ovarian
cancer.
- Secondary Purpose To evaluate the safety of QL1706 in combination with
albumin-binding paclitaxel and bevacizumab in the treatment of platinum-resistant
recurrent ovarian cancer.
Exploratory analysis of the association between the efficacy of the combination regimen
and biomarkers.
Detailed description:
The efficacy of chemotherapy combined with anti-angiogenic agents in the treatment of
platinum-resistant recurrent ovarian cancer has been demonstrated in clinical studies,
and QL1706 acts as a bi-functional combination antibody that blocks both PD-1 and CTLA-4,
in other cancer trials that have been conducted, it is expected that better efficacy and
adverse event rates comparable to those of anti-PD-1 mabs and anti-CTLA-4 mabs will be
achieved with combination chemotherapy and anti-angiogenic drugs, it may be possible to
obtain better anti-tumor effects in platinum-resistant recurrent ovarian cancer patients.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Voluntary signing of a written ICF.
2. Age ≥18 years, ≤75 years, female.
3. The Eastern Cooperative Oncology Group (ECOG) physical fitness score was 0 or 1.
4. Expected survival ≥3 months.
5. Histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube
cancer, or primary peritoneal cancer.
6. Patients with platinum-resistant recurrent ovarian cancer (including fallopian tube
and peritoneal cancer) were defined as progression within 6 months after
platinum-based chemotherapy.
7. At least one measurable lesion according to RECIST v1.1, and this lesion is amenable
to repeated accurate measurements according to RECIST v1.1. Lesions that have
received radiation therapy can be considered as target lesions if they are clearly
progressive and measurable on the basis of imaging.
8. Determination of good organ function through the following requirements:
A) hematology (no blood component and cell growth factor support therapy was used
for 7 days before study initiation) :
I. ANC ≥1.5 × 109 L (1.500 MM3) in absolute neutrophil; II. Platelet count ≥100 ×
109/L (100,000/MM3) ; III. Hemoglobin ≥90 g/L.
B) kidneys:
I. Creatinine clearance * (CrCl) calculated value ≥50 mL/min
* CrCl (Cockcroft-gault formula) will be calculated using Cockcroft-Gault formula
CrCL (mL/min) = [(140-age) × weight (kg) × f ]/(SCR (mg/dL) × 72) F = 0.85; SCR =
serum creatinine. II. Urine protein < 2 + or 24 h (h) urine protein quantification <
1.0 g.
C) liver:
I. Serum total bilirubin (TBil)≤1.5 × ULN II. AST and ALT ≤2.5 × ULN III. Alb
(Alb)≥28GL
D) coagulation function:
I. International standard ratio (INR) and activated partial thromboplastin time
(APTT)≤1.5 × ULN.
E) cardiac function:
I. Left ventricular ejection fraction (LVEF)≥50% .
9. A fertile female subject must have a urine or serum pregnancy test within 3 days
before the first dose (if the urine pregnancy test result can not be confirmed as
negative, a serum pregnancy test is required, whichever is the serum pregnancy
result) , and the results were negative. If a fertile female subject has sex with an
unsterilized male partner, the subject must use an acceptable method of
contraception from the beginning of the screening process, consent must also be
given to the method of contraception used prior to its continued use for 120 days
after the last administration of the study drug; discontinuation of contraception
after this time point should be discussed with the investigator.
10. Subjects were willing and able to comply with schedule visits, treatment protocols,
laboratory tests, and other requirements of the study.
Exclusion Criteria:
1. Ovarian cancer of non-epithelial origin, fallopian tube cancer, primary peritoneal
cancer (such as germ cell tumors) , and low-malignant potential ovarian tumors (such
as borderline tumors) .
2. Previous (within 5 years) or concurrent with other malignancies, the local tumors
that have been cured (such as basal cell skin cancer, squamous cell skin cancer,
superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ,
etc.) and breast cancer that has not recurred for more than 3 years after radical
operation are excluded.
3. Local recurrence is suitable for patients undergoing surgery.
4. Previous radiation therapy of the abdomen and pelvis.
5. Had received immunotherapy in the past, these include immune-checkpoint inhibitors
(such as PD-1 CTLA-4 Bispecific monoclonal antibody, which allow previous use of
PD-1 or PD-L1 mabs) , immune-checkpoint agonists (such as ICOS, CD40, CD137, GITR,
OX40 antibodies, etc.) , and immune-cell therapies for any of the mechanisms of
tumor immunity.
6. Patients who were known to be allergic to any component of any investigational drug,
had a history of severe hypersensitivity to other monoclonal antibody, and were
known to have permanently discontinued the relevant therapeutic drug could not be
enrolled.
7. Participated in the treatment of an experimental drug or used an experimental device
within 4 weeks before the first study administration.
8. One week before the first dose (or 5 drug half-lives, whichever is longer) , a
potent or intermediate CYP3A4 inhibitor, a P-gp or a BCRP inhibitor were received.
9. Last systemic anti-tumor therapy, including chemotherapy, bevacizumab or its
bioanalogues, was given within 3 weeks before the first dose, and anti-tumor hormone
therapy was given within 2 weeks before the first dose Non-target lesions were
treated with palliative local therapy within 2 weeks before the first dose Received
Hapten therapy (such as interleukin, interferon, and thymosin, not including Il-11
for thrombocytopenia) within 2 weeks before the first dose; Within 1 week before the
first administration, she had received Chinese herbal medicine or Chinese patent
medicine with anti-tumor indication.
10. Use of systemic glucocorticoid or other immunosuppressive drug within one week prior
to initial administration, systemic glucocorticoid (i.e. not more than 10mg daily
prednisone or equivalent dose of other glucocorticoid) that do not include nasal
spray, inhalation or other route local glucocorticoid or physiological doses, allow
for symptoms of dyspnea due to diseases such as chronic obstructive pulmonary
disease, and temporary use of glucocorticoid for allergy prevention.
11. The live vaccine was administered within 30 days of the first dose, or was planned
for the duration of the study.
12. Has an active autoimmune disease that requires systemic treatment in the past two
years (such as use of disease-modifying drugs, corticosteroid, immunosuppressive
therapy) , replacement therapy (such as thyroxine, insulin, or physiologic
corticosteroid for adrenal or pituitary insufficiency) is not considered a systemic
treatment.
13. Active or previous history of a well-defined inflammatory bowel disease such as
Crohn's disease, ulcerative colitis or chronic diarrhea.
14. History of immunodeficiency, HIV antibody positive, current long-term use of
systemic corticosteroid or other immunosuppressive agents.
15. Subjects with known active tuberculosis (TB) and suspected active TB should be
excluded by clinical examination.
16. Known active syphilis infection.
17. Known history of organ transplants and Hematopoietic stem cell transplants.
18. Previous history of non-infectious pneumoniainterstitial lung disease requiring
systemic glucocorticoid therapy or current presence of non-infectious pneumonia.
19. Severe infection occurred within 4 weeks before the first dose, including but not
limited to complications, sepsis, or severe pneumonia requiring hospitalization;
Active infection (excluding antiviral therapy for hepatitis B or C) that has
received systemic anti-infective therapy within 2 weeks before the first dose.
20. Untreated subjects with active hepatitis B (HBsAg positive and HBV-DNA > 1000
copies/ml (200 IU/ml or above the lower limit of detection, whichever is higher)
were required to receive anti-hbv therapy during study treatment for those with
hepatitis B; and active hepatitis C subjects (HCV antibody positive and HCV-rna
levels above the lower limit of detection) .
21. Those who had a major surgical procedure or major trauma within 30 days before the
first dose, or who had a major surgical plan within 30 days after the first dose (at
the investigator's discretion) ; Minor local procedures (excluding central venous
catheterization via peripheral venipuncture and intravenous port implantation) were
performed within 3 days before the first dose.
22. Known presence of central nervous system metastases, meningeal metastases, spinal
cord metastases or compression.
23. Subjects with clinical symptoms or repeated drainage of pleural effusion,
pericardial effusion, or ascites.
24. There are currently uncontrolled co-morbidities, these include, but are not limited
to, symptomatic heart failure (grade 2 or higher according to the New York Heart
Association functional class) , unstable angina, acute myocardial ischemia, poorly
controlled arrhythmias, decompensated cirrhosis, nephrotic syndrome, uncontrolled
metabolic disorders, severe active peptic ulcer disease, or gastritis,
psychiatric/social conditions that may limit subjects' ability to comply with
research requirements or affect their ability to provide written informed consent.
25. Uncontrolled hypertension, systolic blood pressure > 140 mmhg or diastolic blood
pressure > 90 mmhg after optimal medical treatment, history of Hypertensive crisis
or hypertensive encephalopathy.
26. Previous history of myocarditis, cardiomyopathy, and malignant arrhythmia. Unstable
angina, myocardial infarction, heart failure or vascular disease (such as a ruptured
aortic aneurysm) that requires hospitalization within 12 months of the first dose,
or other cardiac lesions (such as poorly controlled arrhythmias, myocardial
ischemia) that may affect the safety evaluation of the study drug.
27. Esophageal Gastric varices, severe ulcers, unhealed wounds, gastrointestinal
perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal
abscess, acute gastrointestinal bleeding, extensive bowel resection (partial or
extensive colectomy with chronic diarrhea) , Crohn's disease, ulcerative colitis or
chronic diarrhea.
28. Any arterial thromboembolic event, NCI CTCAE version 5.0 Grade 3 or greater, venous
thromboembolism, transient cerebral ischemia, or cerebrovascular accident occurred
within 6 months before the first dose.
29. Acute exacerbation of chronic obstructive pulmonary disease within 1 month of first
dose.
30. Patients with any sign of bleeding constitution, regardless of severity; patients
with any bleeding or bleeding event ≥ CTCAE grade 3 within 4 weeks before the first
dose.
31. Current imaging or clinical manifestations of gastrointestinal obstruction,
including incomplete obstruction.
32. Severe bleeding tendency or Coagulopathy, or receiving thrombolytic therapy. Aspirin
(> 325mg daily) or dipyrimidine, ticlopidine, clopidogrel, and Cilostazol are
currently used or have been used recently (within 10 days before the first dose of
study treatment) , and anticoagulants that require monitoring of INR (such as
Warfarin) .
33. Imaging showed that the tumor had surrounded or invaded important blood vessels, or
that it was highly likely to invade important blood vessels and cause fatal massive
bleeding during the follow-up study, compression of the superior vena cava, inferior
vena cava or invasion of the heart.
34. Toxicities from previous antitumour therapy did not resolve, defined as toxicities
that did not return to grade 0 or 1 of NCI CTCAE version 5.0, or levels specified in
the inclusion/exclusion criteria; Except for alopecia and sequelae of neurotoxicity
related to previous platinum therapy. For subjects who develop irreversible toxicity
and are not expected to worsen after administration of the study drug (EG, hearing
loss) , it may be included in the study after consultation with the medical
examiner.
35. Local or systemic disease caused by a non-malignant tumor, or disease or symptoms
secondary to the tumor, and can lead to higher medical risk and/or uncertainty in
the evaluation of survival; Such as leukemoid reaction cancer (white blood cell
count > 20 × 10 ^ 9 L) , cachexia (known as weight loss of more than 10% 3 months
before screening) , etc. .
36. Known history of mental illness, substance abuse, alcohol or drug abuse.
37. Women who are pregnant or nursing. The presence of any disease, treatment, or
laboratory abnormality in the past or present may confuse the results of the study,
affect the participant's participation in the study, or may not be in the best
interest of the participant.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Start date:
July 2024
Completion date:
June 2026
Lead sponsor:
Agency:
West China Second University Hospital
Agency class:
Other
Source:
West China Second University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06509971
