Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab

Stopped early · Phase 2

Conditions studied: Urothelial Carcinoma, Bladder Cancer, Myelosuppression Adult, Chemotherapy-induced Neutropenia, Metastatic Bladder Cancer

In brief

This is a Phase 2, multicenter, randomized, open-label study evaluating the safety and efficacy of trilaciclib administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy in participants receiving first-line treatment for advanced/metastatic urothelial carcinoma.

Key facts

Study ID

NCT04887831

Run by

G1 Therapeutics, Inc.

People needed

92

Starts

2021-06-04

Expected to finish

2024-03-01

Last updated by the study team

2025-09-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥18 years
• Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV) (also termed Transitional cell carcinoma [TCC] or Urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
• Participants with mixed histologies are required to have a dominant transitional cell pattern (small cell carcinoma of any proportion is not allowed)
• Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis (N2-N3)
• Measurable disease as defined by RECIST v1.1
• a. Previously irradiated lesions should not be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions.
• Considered to be eligible to receive platinum-based chemotherapy and avelumab maintenance therapy, in the Investigator's judgment
• No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents
• For participants who received prior adjuvant/neoadjuvant chemotherapy for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. If a participant received adjuvant/neoadjuvant chemoradiation for urothelial carcinoma, a treatment-free interval >12 months between last platinum dose and the date of recurrence is required.
• For participants who received prior Immune checkpoint inhibitors (ICI) therapy in the adjuvant/neoadjuvant setting, a treatment-free interval > 3 months between the last dose of ICI and date of recurrence is required.
• Prior local intravesical chemotherapy or immunotherapy is allowed if completed ≥4 weeks prior to the initiation of study treatment
• A formalin-fixed paraffin-embedded (FFPE) tumor tissue block (75-micron) or at least 15 (5-micron) unstained slides from archival or fresh tumor biopsy or resection; the most recent biopsy tissue preferred. Participants who have fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with the Medical Monitor.
• Tumor tissue should be of good quality based on total and viable tumor content. For core-needle biopsy specimens, at least three cores should be submitted for evaluation.
• Transurethral resection of bladder tumor (TURBT) specimens must contain a muscle -invasive component (i.e., T2 or greater) of the bladder tumor as verified by local pathology review. If the TURBT specimens do not contain a muscle-invasive component, then specimens obtained at the time of cystectomy/nephroureterectomy (i.e., pT2 or greater) or metastatic spread (i.e., a sample from a metastatic lesion) will be required prior to randomization. An archival specimen, if available, should also be submitted.
• Participants who do not have tissue specimens that meet eligibility requirements may undergo a biopsy during the screening period. Acceptable samples include core needle biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
• Tumor tissue from bone metastases is not evaluable for programmed death-ligand 1 (PD-L1) expression and is therefore not acceptable.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Adequate organ function as demonstrated by the following laboratory values:
• Hemoglobin ≥9.0 gram per deciliter (g/dL) in the absence of RBC transfusion or ESA administration within 14 days prior to first dose of study drug
• Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L
• Platelet count ≥100 × 10\^9/L
• Estimated glomerular filtration rate ≥ 30 mL/minute/1.73 m\^2
• Total bilirubin ≤1.5 × upper limit of normal (ULN) (<3 ULN if Gilbert's disease)
• ALT and AST ≤2.5 × ULN in the absence of liver metastasis or <5 × ULN in the presence of liver metastasis
• Resolution of nonhematologic toxicities from prior systemic therapy, radiation therapy, or surgical procedures to ≤ Grade 1

You may not qualify if…

• Prior treatment with IL-2, IFN-α, anti-PD-L2, anti-CD137 or CD137 agonists, or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody (including ipilimumab), or any other therapeutic antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways in any setting within 12 months prior to randomization
• Malignancies other than urothelial carcinoma within 2 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration), or other non-clinically significant cancers, which may be considered after discussion with the medical monitor
• Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids. Participant must be off steroids administered for brain metastases for at least 2 weeks prior to the first dose of study drugs. No stereotactic radiation within 1 week or whole-brain radiation within 14 days prior to first dose of study drugs
• Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (≥ Class II New York Heart Association functional classification system), myocardial infarction within 6 months prior to first dose of study drugs, unstable angina, or serious cardiac arrhythmia requiring medication
• QTcF interval > 480 msec. For participants with ventricular pacemakers, QTcF > 500 msec
• Known history of stroke or cerebrovascular accident within 6 months prior to first dose of study drugs
• Known history of serious, chronic active infection (e.g., human immunodeficiency virus, hepatitis B or C, tuberculosis, etc.)
• a. Viral load indicative of HIV, HIV 1/2 antibodies, positive hepatitis B virus surface antigen or hepatitis C virus ribonucleic acid (RNA) if anti-hepatitis C virus antibody screening test positive
• Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
• Therapeutic oral or IV antibiotic use within 2 weeks prior to randomization
• Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease or for dental extraction) are eligible
• Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator's opinion could affect participant safety, compliance, or follow-up in the protocol
• Receipt of any investigational medication within 4 weeks, or at least 5 half-lives, whichever is greater, prior to the first dose of study drugs
• Known hypersensitivity or allergy to study drugs or any component in their formulations
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of asthma symptom control per Global Initiative for Asthma [GINA] 2020)
• Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation
• Radiotherapy to any non-Central nervous system (CNS) site within 1 week prior to the first dose of study drugs, or within 2 weeks to any CNS sites
• Pregnant or lactating women
• a. Women of childbearing potential must have negative serum pregnancy test result within 7 days prior to initiating study treatment
• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study
• Received a live, attenuated vaccine within 4 weeks prior to the first dose of study drugs
• Inactive vaccines, including but not limited to influenza vaccine, pneumococcal vaccine, shingles vaccine, and regionally approved Covid-19 vaccines are allowed
• Participants must agree not to receive a live, attenuated influenza vaccine during study treatment
• History of immune colitis, inflammatory bowel disease, idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted

Where it is running

• Valkyrie Clinical Trial — Los Angeles, California, United States
• The Oncology Institute of Hope and Innovation — Whittier, California, United States
• Rocky Mountain Cancer Centers — Littleton, Colorado, United States
• Florida Cancer Specialists - South — Fort Myers, Florida, United States
• Woodlands Medical Specialists — Pensacola, Florida, United States
• Florida Cancer Specialists - North — St. Petersburg, Florida, United States
• Beacon Cancer Center PLLC — Coeur d'Alene, Idaho, United States
• The Harry and Jeanette Weinberg Cancer Institute — Baltimore, Maryland, United States
• New York Oncology Hematology, P.C. — Albany, New York, United States
• Montefiore Medical Center — The Bronx, New York, United States
• University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States
• Northwest Cancer Specialists, P.C. — Tigard, Oregon, United States
• Tennessee Oncology, PLLC — Nashville, Tennessee, United States
• Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie — Strasbourg, Bas-Rhin, France
• Institut Bergonié - Oncologie Médicale et Pédiatrique — Bordeaux, Gironde, France
• Centre Léon Bérard - Département d'oncologie médicale — Lyon, France
• Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale — Paris, France
• Institut de Cancérologie de Lorraine — Vandœuvre-lès-Nancy, France
• High Technology Hospital MedCenter LTD — Batumi, Adjara, Georgia
• National Center of Urology Named after Laur Managadze — Tbilisi, Georgia
• LTD "Multiprofile Clinic Consilium Medulla" — Tbilisi, Georgia
• Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint — Szolnok, Jász-Nagykun-Szolnok, Hungary
• Országos Onkológiai Intézet — Budapest, Hungary
• Uzsoki Utcai Kórház — Budapest, Hungary
• Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol — Badalona, Barcelona, Spain

Full record on ClinicalTrials.gov

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