RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-06-13

Study Completion:2025-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05335941

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥ 18 years of age at time of screening 2. 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. 3. 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. 4. 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. 5. Patients must have an ECOG performance status ≤ 2. 6. Adequate liver function as defined by AST or ALT ≤ 2.5 x ULN, or ≤ 5 x ULN if documented liver metastases are present. 7. 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. 8. 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. 9. 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) 10. Negative serum or urine pregnancy test at screening for women of child-bearing potential. 11. 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 12. 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. 13. 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.	1. QTc ≥480 msec using Fredericia's QT correction formula 2. Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:

Inclusion Criteria

Exclusion Criteria

1. Age ≥ 18 years of age at time of screening
2. 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.
3. 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.
4. 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.
5. Patients must have an ECOG performance status ≤ 2.
6. Adequate liver function as defined by AST or ALT ≤ 2.5 x ULN, or ≤ 5 x ULN if documented liver metastases are present.
7. 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.
8. 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.
9. 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)
10. Negative serum or urine pregnancy test at screening for women of child-bearing potential.
11. 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
12. 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.
13. 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.

1. QTc ≥480 msec using Fredericia's QT correction formula
2. Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:

Contacts and Locations

Study Contact

Omar Alhalabi, MD

CONTACT

713-745-2740

OAlhalabi@mdanderson.org

Principal Investigator

Omar Alhalabi, MD

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Omar Alhalabi, MD, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-13

Study Completion Date2025-09-30

Study Record Updates

Study Start Date2023-06-13

Study Completion Date2025-09-30

Terms related to this study

Additional Relevant MeSH Terms

Urothelial Carcinoma
Metastatic Cancer