Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-… (NCT06444880) | Clinical Trial Compass
RecruitingPhase 2
Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies
United States40 participantsStarted 2024-10-09
Plain-language summary
To find out if ubamatamab, given by itself or in combination with cemiplimab, can help to control the disease in participants with renal medullary carcinoma (RMC) and epithelioid sarcoma (ES).
Who can participate
Age range
12 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Participants with locally advanced or metastatic RMC (RMC cohort) or ES (ES cohort) histologically confirmed by expert pathology review and loss of SMARCB1 staining by IHC. Participants with advanced or metastatic unclassified renal cell carcinoma with medullary phenotype (a rare SMARCB1 negative RMC variant occurring in individuals without sickle hemoglobinopathies) are also eligible for the RMC cohort.
. Eligible participants should either demonstrate serum CA-125 levels ≥ 70 units/ml during screening or positive H score of \>25 for MUC16 (CA-125) by IHC in tumor tissues collected within 12 months from screening as noted in participant EMR:
. The H score is calculated using the standard formula commonly used in IHC: H score = \[(0 x % negative cells) + (1 x % weak positive cells) + (2 x % moderate positive cells) + (3 x % strong positive cells). For instance, if 50% of tumor cells show weak staining, 30% of tumor cells show moderate staining, and 20% of cells show strong staining, the H-score would be: (50×1)+(30×2)+(20×3)=50+60+60=170.
. If serum CA-125 ≥ 70 units/ml then participants will be enrolled without delay. IHC for MUC16 will be used as a correlative biomarker but not for trial eligibility.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Safety and adverse events (AEs)
Timeframe: Through study completion; an average of 1 year.
. If serum CA-125 \< 70 units/ml then for trial eligibility, MUC16 expression should be checked by IHC in tumor tissues collected within 12 months from screening:
. Participants will be eligible in the RMC cohort regardless of whether they have had prior nephrectomy or still have their primary tumor in-situ.
. Participants must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures ≥ 15 mm with conventional techniques or ≥ 10 mm with more sensitive techniques such as MRI or CT scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
. Participants must have progressed on at least one line of prior therapy.
Exclusion criteria
5. Ability to understand and the willingness to sign a written informed consent document.
. Participants must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, or adequately treated (without recurrence post-resection or post-radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, ductal carcinoma in situ of the breast or low-risk early stage prostate adenocarcinoma with negligible risk of metastasis or death
. Participants previously treated with T-cell-redirecting bispecific antibodies or MUC16-targeted therapies (including vaccines) are excluded. Participants who received CAR-T therapies within 30 days of first dose of study drug are also excluded. However, participants previously treated with immune checkpoint therapies such as anti-PD1, anti-PD-L1, anti-CTLA-4, or anti-LAG-3 immune checkpoint inhibitors are eligible, as long as they have been off these therapies for at least 60 days (\~3 half-lives) prior to initiation of study treatment with ubamatamab.
. Participants currently receiving anticancer therapies or who have received anticancer therapies (including chemotherapy and targeted therapies such as tazemetostat) within 2 weeks (14 days) prior to study Day 1 are excluded. Participants who have completed palliative radiation therapy more than 14 days prior to the first dose of the combination immunotherapy are eligible.
. Participants with persistent grade ≥2 adverse events from prior systemic therapies that would confound timely detection of immune-related adverse events due to ubamatamab and/or cemiplimab or otherwise hinder patient participation in the clinical trial.
. Participants, who have had a major surgery or significant traumatic injury (injury requiring \> 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study drug, participants who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).
. Participants who have organ allografts.
. Known or suspected autoimmune disease. Participants with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus or autoimmune vasculitis \[e.g., Wegener's Granulomatosis\] are excluded from this study. Participants with a history of Hashimoto's thyroiditis only requiring hormone replacement, Type I diabetes, or psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed to participate.