Phase II Trial of Ubamatamab Alone or in Combination With Cemiplimab in MUC16-Expressing SMARCB1-Deficient Malignancies

NCT06444880 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2023-1062NCI-2024-04755
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

SMARCB1-Deficient Malignancies

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (2)

Stage I

EXPERIMENTAL

Stage 1 of study treatment involves being given ubamatamab by itself by vein. The first dose will be given over about 4 hours. Depending on how participants respond, later doses may be given over shorter periods of time (possibly down to 30 minutes per infusion). Participants dose of ubamatamab will be increased from a starting dose on Day 1 to a full dose on Day 15. Participants will receive ubamatamab 1 time every week for the first 4 weeks, then every 3 weeks after that, unless the disease gets worse or intolerable side effects occur. • If the disease gets worse after completing 6 weeks of treatment, participants will move to Stage 2 and receive combination therapy.

Drug: Ubamatamab

Stage 2

EXPERIMENTAL

Participants in Stage 2 will begin receiving ubamatamab and cemiplimab. * If participants are enrolled directly into Stage 2, but did not have therapy with ubamatamab alone, participants will receive ubamatamab 1 time each week for 4 weeks, before beginning combination therapy. * If participants have already completed Stage 1 and are moving on to Stage 2, participants will begin with combination therapy. During Stage 2, ubamatamab is given by vein over 30 minutes to 4 hours, as described above. Cemiplimab is given by vein over 30 minutes.

Drug: Ubamatamab; Drug: Cemiplimab

Interventions

Ubamatamab DRUG

Given by IV

Stage 2; Stage I

Cemiplimab DRUG

Given by IV

Stage 2

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• i. If H score is \< 25 then the patient will not be eligible for the trial ii. If H score ≥ 25 then the patient will be eligible for the trial
• 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.
• There must be evidence of progression on or after last treatment regimen received.
• ECOG performance status 0-1
• a. NOTE: If participant is unable to walk due to paralysis, but is mobile in a wheelchair, participant is considered to be ambulatory for the purpose of assessing their performance status.
• Age (at the time of consent/assent): ≥ 18 years
• a. RMC is the third most common renal cell carcinoma in children and young adults in the United States21 and while we will initially enroll participants aged ≥18 years old, we will in coordination with Regeneron consider allowing pediatric participants ≥12 years old if no trial limiting toxicities (TOX), as defined in Section 9.1.2., after the interim analysis of the first 10 participants enrolled and based on the accumulated pharmacokinetic / pharmacodynamic data of ubamatamab in this population at that time. If these criteria are fulfilled, then adolescent participants age 12 years and older will be allowed with signed assent and parental consent according to institutional guidelines and requirements, as long as their weight is \>40 kg given that this is the lower weight limit for which safety following ubamatamab with or without cemiplimab exposure has been ascertained.
• Consent to MD Anderson companion laboratory protocol 2014-0938

You may not qualify if:

• 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.
• Uncontrolled infection with human immunodeficiency virus, hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency.
• Participants with HIV who have controlled infection (undetectable viral load with the exception of clinically insignificant blips and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted.
• Participants with hepatitis B surface antigen positive (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving antiviral therapy for hepatitis B) are permitted.
• Participants with HBsAg negative but total HBV core antibody positive (HBc Ab+) are permitted with the following requirements: Serum HBV DNA PCR should be tested and if it is above the limit of detection at screening then antiviral therapy for HBV must be initiated prior to study entry. If serum HBV DNA PCR is below the limit of detection periodic monitoring of HBsAg must be performed every 12 months +/- 3 months.
• Participants who are Hepatitis C virus antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
• Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea, uncontrolled nausea or vomiting. Patients with active COVID-19 disease as indicated by a positive polymerase reaction (PCR) test are excluded. Participants with previous COVID-19 disease are allowed if ≥30 days from last positive test, and COVID-19 symptoms have resolved and/or PCR test is now negative.
• Participants must not be scheduled to receive another experimental drug while on this study.
• Participants who are on high dose steroid (e.g., \> 10mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g., infliximab). Topical, inhaled, intra-articular, ocular, or intranasal corticosteroids (with minimal systemic absorption) are allowed. A brief course (\<48 hours) of systemic corticosteroids for prophylaxis (eg, from contrast dye allergy) is permitted. Physiological corticosteroid replacement therapy for adrenal insufficiency (up to hydrocortisone 30 mg / daily or equivalent) is also permitted.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

• Connolly DM, Revon-Riviere G, Chami R, Mills D, Coblentz AC, Uldrick TS, Knorr DA, Goncalves P, Dobosz M, Jalal S, Cohen-Gogo S, Morgenstern DA. Mucin 16-Directed Therapy in Pediatric Sarcomas: Case Evidence of Ubamatamab Efficacy in Epithelioid Sarcoma and Its Implications for Other Sarcoma Subtypes. JCO Precis Oncol. 2025 Aug;9:e2500404. doi: 10.1200/PO-25-00404. Epub 2025 Aug 1.

  PMID: 40749151 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

cemiplimab

Study Officials

• Pavlos Msaouel, MD,PHD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pavlos Msaouel, MD,PHD,PHD

CONTACT

(713) 563-4585; pmsaouel@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2024
• First Posted: June 6, 2024
• Study Start: October 9, 2024
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

US (1)