Ubamatamab + Cemiplimab for Tumors

Overseen By Pavlos Msaouel, MD,PHD,PHD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: T-cell-redirecting, MUC16-targeted, CAR-T, others

Disqualifiers: Other malignancies, Autoimmune disease, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug ubamatamab (a bispecific monoclonal antibody), alone or with cemiplimab (an immunotherapy drug), can help manage renal medullary carcinoma (a rare kidney cancer) and epithelioid sarcoma (a type of soft tissue cancer). The trial consists of two stages: Stage 1 tests ubamatamab alone, while Stage 2 tests the combination of both drugs. Candidates for this trial include individuals with confirmed renal medullary carcinoma or epithelioid sarcoma who have experienced disease progression after previous treatments and have at least one measurable tumor site. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you are currently receiving anticancer therapies or have received them within 2 weeks prior to the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ubamatamab, whether used alone or with cemiplimab, has been safe in previous studies. Ubamatamab alone caused manageable side effects. In combination with cemiplimab, the treatment was well-tolerated, even in patients with extensive prior treatments for ovarian cancer. This indicates that patients generally handled the treatment without major issues. While these results are encouraging, side effects can vary from person to person. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ubamatamab and cemiplimab because they offer a novel approach to treating tumors. Unlike traditional treatments that might rely on chemotherapy or radiation, ubamatamab is an antibody that targets specific cancer cells, potentially minimizing damage to healthy cells. Cemiplimab, on the other hand, is an immunotherapy drug that blocks a protein called PD-1, enabling the immune system to better attack cancer cells. The combination of these two treatments is particularly promising as it harnesses both targeted therapy and immune system activation, potentially leading to more effective and less toxic treatment outcomes for patients.

What evidence suggests that this trial's treatments could be effective for renal medullary carcinoma and epithelioid sarcoma?

In this trial, participants will receive ubamatamab, which previous studies have shown to be promising by targeting a protein called MUC16 on cancer cells. This protein aids the immune system in recognizing and attacking cancer. Research indicates that ubamatamab alone has produced positive responses in patients with MUC16-positive tumors. In Stage 2 of this trial, participants will receive a combination of ubamatamab and cemiplimab, a drug that also boosts the immune response. Earlier studies have demonstrated that this combination has acceptable safety and effectiveness in patients who have undergone many treatments. This suggests that the combination might effectively tackle tough cancers, such as renal medullary carcinoma and epithelioid sarcoma, by enhancing the body's immune defense against them. ^{4 6 7 8 9}

Who Is on the Research Team?

Pavlos Msaouel

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with specific tumors known as renal medullary carcinoma (RMC) and epithelioid sarcoma (ES). Participants must express a protein called MUC16 and lack another protein, SMARCB1, in their tumors.

Inclusion Criteria

I am eligible whether or not I've had my kidney removed due to cancer.

Consent to MD Anderson companion laboratory protocol 2014-0938

I have at least one tumor that can be measured.

Exclusion Criteria

Participants with known or suspected autoimmune disease

I have received an organ transplant from another person.

I have not had major surgery or significant injury in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Participants receive ubamatamab by itself, starting with a dose on Day 1 and increasing to a full dose on Day 15. Ubamatamab is administered weekly for the first 4 weeks, then every 3 weeks.

6 weeks

Weekly visits for the first 4 weeks, then every 3 weeks

Stage 2 Treatment

Participants receive combination therapy with ubamatamab and cemiplimab. Ubamatamab is given weekly for 4 weeks if not previously received, followed by combination therapy.

Variable, depending on disease progression

Weekly visits for ubamatamab, then combination therapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Ubamatamab

Trial Overview The study is testing the effectiveness of a drug named Ubamatamab alone or when used together with another drug called Cemiplimab. The goal is to see if these treatments can control the disease in patients.

How Is the Trial Designed?

Group I: Stage I Experimental Treatment 1 Intervention

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.

Group II: Stage 2 Experimental Treatment 2 Interventions

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.

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., et al.[2023]

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

Bispecific antibodies, like catumaxomab and blinatumomab, are emerging as effective therapeutics, with two already approved for use and over 30 more in clinical development, primarily targeting cancer treatment by retargeting T cells to attack tumor cells.

The diverse designs of bispecific antibodies, with over 60 different formats, allow for customization in their mechanisms of action, enhancing their potential effectiveness in various clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative molecular formats and therapeutic applications for bispecific antibodies. Spiess, C., Zhai, Q., Carter, PJ.[2021]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

Catumaxomab, a trispecific antibody approved for treating EpCam positive gastric and ovarian tumors, is no longer available in the European market due to production issues, despite its FDA orphan drug status.

Blinatumomab, a bispecific T cell engager antibody approved for relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), highlights the potential of bispecific antibodies, with over 50 currently in clinical trials for various cancers, aiming to expand treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies for cancer therapy: A review. Krishnamurthy, A., Jimeno, A.[2019]

Cemiplimab is the first FDA-approved treatment for patients with advanced cutaneous squamous cell carcinoma (CSCC) who cannot undergo curative surgery or radiation, demonstrating rapid and substantial antitumor efficacy in phase II clinical trials.

The treatment has an acceptable safety profile, with low rates of treatment discontinuation (7%) and death (3%), although current recommendations are based mainly on phase II data due to the lack of an approved comparator agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab in advanced cutaneous squamous cell carcinoma. Naik, PP.[2022]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

The novel bispecific tribodies (TR0304 and TR0506) demonstrated similar binding affinity to their targets as existing monoclonal antibodies but showed enhanced lymphocyte activation and greater in vitro cytotoxicity against tumor cells compared to traditional combination therapies.

These tribodies may offer advantages over conventional treatments, including lower production costs and reduced dosage requirements, making them promising candidates for treating cancer patients who are resistant to current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of the Antitumor Efficacy of Novel Multi-Specific Tribodies with Combinations of Approved Immunomodulatory Antibodies. Manna, L., Rapuano Lembo, R., Yoshioka, A., et al.[2023]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

REGN4018, a bispecific antibody targeting MUC16 on ovarian cancer cells and CD3 on T cells, effectively activates T cells to kill tumor cells in vitro and shows potent antitumor activity in preclinical models, including immunocompetent mice.

Toxicology studies in cynomolgus monkeys indicated that REGN4018 has good tolerability, with only minimal and transient increases in serum cytokines and no significant toxicity, supporting its potential for clinical evaluation in patients with advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Mucin 16 bispecific T cell-engaging antibody for the treatment of ovarian cancer. Crawford, A., Haber, L., Kelly, MP., et al.[2020]

Bispecific antibodies, like Removab and Blincyto, have shown significant potential in immuno-oncology, leading to increased interest and investment from pharmaceutical companies.

Currently, over 30 bispecific molecules are in clinical trials, highlighting their growing role as immune effector cell engagers in cancer treatment, with promising strategies targeting various immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? Del Bano, J., Chames, P., Baty, D., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11627180/

Translational findings support regimen selection for first‐in ... Ubamatamab, a MUC16 × CD3 bispecific antibody that promotes T‐cell‐mediated cytotoxicity of MUC16‐expressing cells, is being evaluated in a first‐in‐human (FIH ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24114028

Ovarian Cancer PO011LBA/#1512 Ubamatamab ... All patient tumors expressed MUC16 by immunohistochemistry. Responses with ubamatamab monotherapy were observed across a range of MUC16 expression levels.

3. asco.org asco.org/abstracts-presentations/ABSTRACT451926

A phase 1/2 study of ubamatamab (REGN4018), a MUC16 ... A phase 1/2 study of ubamatamab (REGN4018), a MUC16×CD3 bispecific antibody, administered alone or in combination with cemiplimab (anti–PD-1) in patients with ...

4. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(24)00777-7/fulltext

A phase I/II study of ubamatamab (REGN4018) ... Ubamatamab (REGN4018) is a MUC16 x cluster of differentiation 3 (MUC16xCD3) bispecific antibody that bridges MUC16 on tumor cells and CD3 on T cells to promote ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03564340

NCT03564340 | Study of REGN4018 (Ubamatamab) ... The main purpose of this study is to: Learn about the safety of ubamatamab and to find out what dose of ubamatamab can be given alone or with cemiplimab to ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5632

A phase 1/2 study of ubamatamab (REGN4018), a MUC16 ... Ubamatamab is a MUC16 × cluster of differentiation 3 (MUC16×CD3) bispecific antibody that bridges MUC16 on tumor cells and CD3 on T cells to promote T-cell– ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39652449/

Translational findings support regimen selection for first-in- ... Ubamatamab, a Mucin 16 (MUC16) × cluster of differentiation 3 (CD3) bispecific antibody that promotes T-cell-mediated cytotoxicity of MUC16-expressing cells ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03564340

NCT03564340 | Study of REGN4018 (Ubamatamab) ... The main purpose of this study is to: Learn about the safety of ubamatamab and to find out what dose of ubamatamab can be given alone or with cemiplimab to ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02770-9/fulltext

754P Ubamatamab (MUC16xCD3 bispecific antibody) with ... In phase 1 (NCT03564340), ubamatamab monotherapy resulted in an acceptable safety profile and durable responses. We now present ubamatamab combined with ...