Trial Title:
Safety and Efficacy of Targeting PP2A in Ovarian Clear Cell Carcinoma Using Dostarlimab and LB-100
NCT ID:
NCT06065462
Condition:
Ovarian Clear Cell Carcinoma
Conditions: Official terms:
Carcinoma
Adenomyoepithelioma
Adenocarcinoma, Clear Cell
Dostarlimab
LB100
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dostarlimab
Description:
Given by vein (IV)
Arm group label:
Dostarlimab + LB-100
Intervention type:
Drug
Intervention name:
LB-100
Description:
GIven by vein (IV)
Arm group label:
Dostarlimab + LB-100
Summary:
To learn if the combination of dostarlimab and LB-100 can help to control ovarian clear
cell carcinoma
Detailed description:
Primary Objectives:
1. To estimate overall survival in patients with recurrent ovarian clear cell carcinoma
being treated with LB-100 and dostarlimab, including specific survival probabilities
at 6 and 12 months.
Secondary Objectives:
1. To describe clinically significant and immune related adverse events (ir-AEs) in the
study population.
2. To determine the objective response rate (ORR), time to initial response,
progression free survival (PFS), and duration of response (DOR) using modified
RECIST v1.1 criteria.
a. Although the clinical benefit of these drugs has not yet been established, the
intent of offering this treatment is to provide a possible therapeutic benefit, and
thus the patient will be carefully monitored for tumor response and symptom relief
in addition to safety and tolerability.
3. Translational:
1. To describe PP2A activity and immune changes, using baseline and on-treatment
tumor biopsies and peripheral blood mononuclear cells (PBMCs)
2. To describe expression of mismatch repair proteins using immunohistochemistry
(IHC)
3. To correlate circulating tumor DNA (ctDNA) levels with response by modified
RECIST v1.1 criteria.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Inclusion criteria will be assessed within 28 days of starting study treatment:
1. Ability to provide signed informed consent
2. Age 18-75 years at time of study entry
3. Willingness and ability to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including
follow up
4. Histology showing recurrent clear cell ovarian, peritoneal, or fallopian tube cancer
(mixed histology with predominant clear cell component is acceptable).
5. Receipt of at least one prior line of therapy for recurrent disease or development
of platinum resistant or refractory disease, defined by progression of disease on a
platinum-containing regimen or recurrence of disease within 180 days of previous
platinum treatment
6. Available somatic mutation testing results (CLIA source) that reveal no PPP2R1A
mutations
7. Measurable disease based on modified RECIST v1.1. For the purposes of this study
measurable disease is defined at least one "target lesion" that can be accurately
measured in at least one dimension (longest dimension to be recorded). Each target
lesion must be >20 mm when measured by conventional techniques, including palpation,
plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or >10
mm when measured by spiral CT. The target lesion must be distinct from other tumor
areas selected for pre-treatment biopsies. Second lesion selected for pre-treatment
biopsy must be biopsy accessible.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. See Section
14.
9. Life expectantly of ≥12 weeks
10. Adequate normal organ and bone marrow function as defined below.
1. Hemoglobin ≥8.0 g/ dL
2. Absolute neutrophil count (ANC) ≥ 1000/mm3
3. Platelet count ≥100 x 109/L (>100,000/mm3)
4. Serum bilirubin ≤1.5 x ULN. This will not apply to patients with confirmed
Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is
predominantly unconjugated in the absence of hemolysis or hepatic pathology),
who will be allowed only in consultation with their physician.
5. AST (SGOT)/ALT (SGPT) ≤2.5 x ULN unless liver metastases are present, in which
case it must be ≤5 x ULN
6. Measured creatinine clearance (CL) ≥ 50 mL/min or Calculated creatinine CL ≥ 50
mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine
(mg/dL)
11. Evidence of post-menopausal status or negative serum pregnancy test for female
pre-menopausal patients. The effects of dostarlimab and LB-100 on the developing
human fetus are unknown. For this reason, women of child-bearing potential must
agree to use adequate contraception (See Section 5.6.2).
12. Women will be considered post-menopausal if they have been amenorrheic for 12 months
without an alternative medical cause. The following age-specific requirements apply:
1. Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing and follicle-stimulating hormone levels
in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy)
2. Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or
hysterectomy)
Exclusion Criteria:
Exclusion criteria will be assessed within 28 days of starting study treatment:
1. Participation in another clinical study with an investigational product (IP) during
the last 28 days.
2. Prior treatment with anti-CTLA-4 or anti-PDL-1/PD-1 antibodies.
3. Patients with mismatch repair deficient (dMMR) by IHC or microsatellite
instability-high tumors
4. Concurrent treatment on another clinical study, unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.
5. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization,
monoclonal antibodies) ≤21 days prior to the first dose of study drug. If sufficient
wash-out time has not occurred due to the schedule or PK properties of the agent, a
longer wash-out period will be required, as agreed by study sponsors and the
investigators.
6. Any unresolved toxicity NCI CTCAE Grade 2 from previous anticancer therapy with the
exception of 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 principal investigator.
2. Subjects with irreversible toxicity not reasonably expected to be exacerbated
by the treatment with investigational therapy may be included only after
consultation with the primary investigator.
7. Any concurrent chemotherapy, immunotherapy, or hormonal therapy for cancer
treatment.
8. Major surgical procedure (defined by the investigator) within 28 days prior to the
first dose of treatment. Note: Local surgery of isolated lesions for palliative
intent is acceptable.
9. History of allogenic or hematologic organ transplantation.
10. Active or prior documented autoimmune or inflammatory disorders, including
inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis in the
last 6 months (with the exception of diverticulosis), systemic lupus erythematosus,
Sarcoidosis syndrome, or Wegener syndrome.
a. The following exceptions to this criterion are listed below. i. Subjects with
vitiligo or alopecia. ii. Subjects with hypothyroidism stable on hormone
replacement. iii. Any chronic skin condition that does not require systemic therapy.
iv. Subjects without active disease in the last 5 years may be included but only
after consultation with the primary investigator.
v. Subjects with celiac disease controlled by diet alone
11. Uncontrolled intercurrent illness, including but not limited to: ongoing or active
infection; symptomatic congestive heart failure; uncontrolled hypertension; unstable
angina pectoris; cardiac arrythmia; interstitial lung disease; chronic obstructive
pulmonary disease requiring systemic steroid therapy, oxygen, or hospitalization;
serious chronic gastrointestinal conditions associated with diarrhea; or psychiatric
illness/social situations that would limit compliance with study requirement,
substantially increase risk of incurring AEs, or compromise the ability of the
patient to give written informed consent.
12. Any medical, social, or psychological condition that would interfere with evaluation
of study treatment or interpretation of participant safety or study results.
13. 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, or HBsAg, result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
1. Subjects with a past or resolved HBV infection (defined as presence of
hepatitis B core antibody, or anti-HBc, and absence of HBsAg) are eligible.
2. Subjects positive for hepatitis C (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV RNA.
3. Patients with positive results of HIV that meet all of the following
eligibility criteria may be enrolled:
i. Have a T-cell (CD4+) count ≥350 cells/µL ii. No history of opportunistic
infections or other malignancies iii. Have an HIV viral load less than 400 copies/mL
prior to enrollment iv. In the opinion of the investigator, their antiretroviral
therapy (ART) or other HIV treatments will not interfere with the activity of the
investigational product or cause any confusion with the assessment of the
investigational drug toxicities
14. History of another primary malignancy except for the following histories:
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of treatment and of low potential risk of
recurrence.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
15. History of leptomeningeal carcinomatosis.
16. Untreated brain metastases or spinal cord compression. Subjects with suspected brain
metastases at screening should have an MRI (preferred) or CT preferably with IV
contrast of the brain prior to study entry.
a. Subjects with treated brain metastasis as evidenced by stable findings on brain
MRI performed 4-6 weeks after completion of treatment would be eligible.
17. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms
18. Current or prior use of immunosuppressive medication within 14 days before the first
dose of trial therapies. Listed below are the exceptions to this criterion.
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra-articular infection)
2. Systemic corticosteroids at physiologic doses not to exceed 10mg/day of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
19. Receipt of live attenuated vaccine within 30 days prior to the first dose of
treatment. Note: subjects, if enrolled, should not receive live vaccines whilst
receiving treatment and up to 90 days after the last dose of treatment
20. Female subjects who are pregnant or breastfeeding or of reproductive potential who
are not willing to employ effective birth control from screening to 180 days after
the last dose of treatment
a. Pregnant women are excluded from this study because the investigational agents
have unknown teratogenic or abortifacient effects. Because there is also an unknown
but potential risk for adverse events in nursing infants secondary to treatment of
the mother with these agents, breastfeeding should be discontinued.
21. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients
22. Unresolved partial or complete small or large bowel obstruction
23. Judgment by the investigator that the patient is unsuitable to participate in the
study or that the patient is unlikely to comply with study procedures, restrictions,
and requirements
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ljiljana Milojevic
Phone:
713-792-8578
Email:
lmilojev@mdanderson.org
Investigator:
Last name:
Amir Jazaeri, M D
Email:
Principal Investigator
Start date:
November 10, 2023
Completion date:
January 31, 2026
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
GSK Pharma
Agency class:
Other
Collaborator:
Agency:
Lixte
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06065462
http://www.mdanderson.org
