Urothelial CarcinomaPhase 2NCT05335941
A Phase 2 Study to Evaluate the Triplet Combination of Pemetrexed Plus AB928 (Etrumadenant) + AB122 (Zimberelimab) in Patients With Previously Treated Advanced or Metastatic MTAP Deficient Urothelial Carcinoma
A Phase 2 study testing Pemetrexed, Zimberelimab and Etrumadenant in people with Urothelial Carcinoma and Metastatic Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This is a Phase 2 open-label, single-arm trial for patients with MTAP-deficient advanced urothelial cancer who had received prior immunotherapy. This is a single site study at the University of Texas MD Anderson Cancer Center. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma, Metastatic Cancer
- What is being tested?
- Pemetrexed, Zimberelimab and Etrumadenant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2023to 30 Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years of age at time of screening
- Patients must have histologic confirmation of MTAP-deficient metastatic urothelial carcinoma. MTAP-deficiency must be verified by institutional CLIA-certified IHC or by Next gen sequencing (such as FoundationOne or MDACC genomic analysis) showing copy number loss of MTAP gene. Histological variants such as glandular, squamous, sarcomatoid, micropapillary, plasmacytoid, and small cell changes will be allowed for this trial if these tumors are MTAP-deficient.
- Patients can be considered for second line of therapy or beyond (after ICI with PD-(L)1 agent). Any prior intravesical therapy is allowed and does not count as a prior line of therapy.
- All patients must have measurable disease by RECIST v1.1 and tumors of sufficient sizes for biopsy. In general, liver and lung lesions should be at least 1.0 cm, and patients with lymph node-only disease should have lesions of ≥ 1.5 cm in shortest dimension.
- Patients with disease confined to bone may be eligible if a measurable lytic defect is present. The study PI is the final arbiter in questions related to measurability. Patients with a three-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease.
- Patients must have an ECOG performance status ≤ 2.
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- Adequate liver function as defined by AST or ALT ≤ 2.5 x ULN, or ≤ 5 x ULN if documented liver metastases are present.
- Total bilirubin ≤ 1.5 x ULN, except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin ≤ 3.0 mg/dL.
- Adequate bone marrow reserves as define by an ANC ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dL (may have been transfused), and platelets ≥ 100 x 109/L.
- Adequate renal function as defined by a normal serum creatinine, or a creatinine clearance ≥ 45 ml/min [either measured using a 24 hour urine, calculated using CockroftGault, or estimated using the MDRD method from the National Kidney Disease Education Program (NKDEP) (the method reported by MDACC laboratories)] Cockroft-Gault formula: CrCl = [(140-age) • wt(kg)]/[72 •Creat (mg/dL)] (Multiply by 0.85 for females)
- Negative serum or urine pregnancy test at screening for women of child-bearing potential.
- Female participants of reproductive potential, defined as not surgically sterilized and between menarche and 1 year post menopause, must have a negative serum pregnancy test within 4 weeks prior to initiation of study treatment
- Female participants of reproductive potential and male participants with female partners of reproductive potential must remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive measures from the start of study treatment until 30 days after the last dose of etrumadenant, 90 days after the last dose of zimberelimab, 180 days after the last dose of pemetrexed, whichever is longer.
- Please refer to appendix 5
- The ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Pemetrexed. The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.
- Mild autoimmune conditions (such as localized psoriasis or vitiligo) requiring minimal treatment or systemic autoimmune conditions well controlled by target agents such as an anti-IL-17 that do not affect overall immune system. Patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, Type I diabetes, or conditions not expected to recur in the absence of an external trigger are allowed to participate.
- Prior anti-PD-1/PD-L1 therapy is mandatory
Who cannot join
- QTc ≥480 msec using Fredericia's QT correction formula
- Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:
- Treatment with known BCRP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of and throughout study treatment b. Treatment with known P-gp substrates with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment c. Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) and strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment d. Refer to the following for more examples of relevant substrates, inhibitors, and inducers with the potential for drug-drug interactions with etrumadenant: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers
- Any gastrointestinal condition that would preclude the use of oral medications (e.g., difficulty swallowing, nausea, vomiting, or malabsorption)
- Prior treatment with an agent targeting the adenosine pathway
- History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
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- Primary central nervous system (CNS) malignancies or CNS metastases, including leptomeningeal metastases, are not allowed. Subjects with previously treated brain metastases will be allowed if the brain metastases have been stable for at least 4 weeks following prior treatment and no ongoing steroid requirement.
- Any other malignancy from which the patient has been disease-free for less than 2 years, except for non-melanomatous skin cancer, controlled localized prostate cancer, controlled thyroid papillary carcinoma, and in situ carcinoma of any site.
- Women who are pregnant or breastfeeding or intend to become pregnant during their participation in the study.
- Presence of large third space fluid which cannot be controlled by drainage. For patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of Pemetrexed therapy, consideration should be given to draining the effusion prior to dosing. However, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy.
- Patients with active 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.
- Any condition requiring systemic treatment with corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids, steroids as premeds for hypersensitivity reactions, and adrenal replacement steroids doses ≤10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- History of primary immunodeficiency.
- Patients who have prior organ transplantation, including allogeneic stem-cell transplant.
- Live vaccinations within 4 weeks of the first dose of therapy and while on trials is prohibited. Receiving a COVID-19 vaccine at any timepoint will not result in exclusion from the trial.
- True positive test results for active hepatitis A, B, or C during screening.
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, symptomatic cardiac arrhythmia, or interstitial lung disease.
- Uncontrolled psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
- Known allergy or hypersensitivity to study drug formulations.
- Major surgical procedure (as defined by the PI or co-PIs within 28 days prior to the first dose of therapy) or still recovering from prior surgery.
- Patient currently on dialysis.
- Patients who had to discontinue checkpoint therapy due to grade 4 toxicity in the past
- Prior antifolate therapy in the context of neoadjuvant chemotherapy or metastatic disease.
Trial locations and contacts
1 site in 1 country.
About this study
This is a Phase 2 open-label, single-arm trial for patients with MTAP-deficient advanced urothelial cancer who had received prior immunotherapy. This is a single site study at the University of Texas MD Anderson Cancer Center. This study will allow patients in second line of treatment for advanced urothelial ca or beyond. All patients must have been previously treated with immune checkpoint inhibitor (ICI) therapy as per current standard of care.
Read the detailed description
Objectives:
Primary Objectives:
- To evaluate the safety and tolerability of the triplet combination regimen.
- To evaluate the clinical activity of the triplet combination regimen.
Secondary Objectives:
- To explore the biological changes in MTAP-deficient UC tumor microenvironment including peripheral T-cells, tumor-infiltrating T-cells, macrophages, and myeloid-derived suppressor cell (MDSCs)
Exploratory objective:
- To evaluate survival of patients treated with triplet combination regimen.
- Conditions
- Urothelial Carcinoma, Metastatic Cancer
- Being tested
- Pemetrexed, Zimberelimab, Etrumadenant
- Medical subject headings
- Carcinoma, Transitional Cell, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemetrexedDrug
Also called LY23151, Alimta®, MTA, Multitargeted Antifolate
Given by vein (IV)
ZimberelimabDrug
Also called AB122
Given by vein (IV)
EtrumadenantDrug
Also called AB928, Etruma
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Pemetrexed Plus AB928 (Etrumadenant) Plus AB122 (Zimberelimab) | Experimental | All patients will receive combination therapy of pemetrexed and ZIMBERELIMAB (AB122) intravenously every 3 weeks as well as ETRUMADENANT (AB928) orally daily. Receives: Drug: Pemetrexed; Drug: Zimberelimab; Drug: Etrumadenant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and Number of Participants With Complete or Partial Response as their Best Overall Response per RECIST v1.1.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start13 Jun 2023
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Omar Alhalabi, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05335941
- Sponsor's protocol ID
- 2021-0774
- Other IDs
- NCI-2022-02708
- Status last verified
- Aug 2026
- First submitted
- 24 Mar 2022
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study to Evaluate the Triplet Combination of Pemetrexed Plus AB928 (Etrumadenant) + AB122 (Zimberelimab) in Patients With Previously Treated Advanced or Metastatic MTAP Deficient Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT05335941
- Acronym / sponsor ID
- 2021-0774
- Conditions
- Urothelial Carcinoma, Metastatic Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 10 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 13 Jun 2023 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 20 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2 open-label, single-arm trial for patients with MTAP-deficient advanced urothelial cancer who had received prior immunotherapy. This is a single site study at the University of Texas MD Anderson Cancer Center. This study will allow patients in second line of treatment for advanced urothelial ca or beyond. All patients must have been previously treated with immune checkpoint inhibitor (ICI) therapy as per current standard of care.
Detailed description
Objectives:
Primary Objectives:
- To evaluate the safety and tolerability of the triplet combination regimen.
- To evaluate the clinical activity of the triplet combination regimen.
Secondary Objectives:
- To explore the biological changes in MTAP-deficient UC tumor microenvironment including peripheral T-cells, tumor-infiltrating T-cells, macrophages, and myeloid-derived suppressor cell (MDSCs)
Exploratory objective:
- To evaluate survival of patients treated with triplet combination regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pemetrexed Plus AB928 (Etrumadenant) Plus AB122 (Zimberelimab) | Experimental | Drug: Pemetrexed, Drug: Zimberelimab, Drug: EtrumadenantAll patients will receive combination therapy of pemetrexed and ZIMBERELIMAB (AB122) intravenously every 3 weeks as well as ETRUMADENANT (AB928) orally daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age ≥ 18 years of age at time of screening
- Patients must have histologic confirmation of MTAP-deficient metastatic urothelial carcinoma. MTAP-deficiency must be verified by institutional CLIA-certified IHC or by Next gen sequencing (such as FoundationOne or MDACC genomic analysis) showing copy number loss of MTAP gene. Histological variants such as glandular, squamous, sarcomatoid, micropapillary, plasmacytoid, and small cell changes will be allowed for this trial if these tumors are MTAP-deficient.
- Patients can be considered for second line of therapy or beyond (after ICI with PD-(L)1 agent). Any prior intravesical therapy is allowed and does not count as a prior line of therapy.
- All patients must have measurable disease by RECIST v1.1 and tumors of sufficient sizes for biopsy. In general, liver and lung lesions should be at least 1.0 cm, and patients with lymph node-only disease should have lesions of ≥ 1.5 cm in shortest dimension.
- Patients with disease confined to bone may be eligible if a measurable lytic defect is present. The study PI is the final arbiter in questions related to measurability. Patients with a three-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease.
Key exclusion criteria (24 listed)
- QTc ≥480 msec using Fredericia's QT correction formula
- Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:
- Treatment with known BCRP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of and throughout study treatment b. Treatment with known P-gp substrates with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment c. Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) and strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment d. Refer to the following for more examples of relevant substrates, inhibitors, and inducers with the potential for drug-drug interactions with etrumadenant: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers
- Any gastrointestinal condition that would preclude the use of oral medications (e.g., difficulty swallowing, nausea, vomiting, or malabsorption)
- Prior treatment with an agent targeting the adenosine pathway
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PemetrexedAlso: LY23151, Alimta®, MTA, Multitargeted AntifolateGiven by vein (IV) | Drug | Pemetrexed Plus AB928 (Etrumadenant) Plus AB122 (Zimberelimab) |
| ZimberelimabAlso: AB122Given by vein (IV) | Drug | Pemetrexed Plus AB928 (Etrumadenant) Plus AB122 (Zimberelimab) |
| EtrumadenantAlso: AB928, EtrumaGiven by PO | Drug | Pemetrexed Plus AB928 (Etrumadenant) Plus AB122 (Zimberelimab) |
Primary outcome
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and Number of Participants With Complete or Partial Response as their Best Overall Response per RECIST v1.1.
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Omar Alhalabi, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pemetrexed, Zimberelimab and Etrumadenant in people with Urothelial Carcinoma and Metastatic Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 and Number of Participants With Complete or Partial Response as their Best Overall Response per RECIST v1.1. (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.