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

NCT04887831 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: G1T28-2092021-000205-24IND: 156967
• Study Type: interventional
• Target: 92
• Locations: 5 countries
• Sites: 34

Brief Summary

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.

Conditions

Urothelial Carcinoma; Bladder Cancer; Myelosuppression Adult; Chemotherapy-induced Neutropenia; Metastatic Bladder Cancer

Keywords

Trilaciclib dihydrochloride/Cosela; Metastatic Urothelial Carcinoma; Cyclin-dependent kinase 4/6 inhibitor; Immuno-oncology; Solid tumor; Chemotherapy-induced myelosuppression; Myeloprotective

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progression-Free Survival (PFS) During Overall Study

  The PFS was defined as the time from date of randomization to the date of the first documented disease progression, or death in the absence of PD for those who had a PFS event, and the time from randomization to the censoring date for those who did not have a PFS event.

  From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks

Secondary Outcomes (13)

• Number of Participants With Objective Response Rate (ORR) During Chemotherapy Period

  From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks

• Number of Participants With Objective Response Rate During Overall Treatment Period

  From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks

• Percentage of Participants Survived at 12 Months [Overall Survival (OS) Rate]

  From date of randomization (Day 1) up to Month 12

• Myeloprotective Effects

  Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy, approximately up to 4 months

• Disease Control Rate (DCR) During Maintenance Period

  From date of randomization, up to 12 cycles (21-day each) of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the participant or investigator, assessed up to 34 weeks.

Study Arms (2)

Platinum-based chemotherapy followed by avelumab maintenance therapy

ACTIVE COMPARATOR

Gemcitabine 1000 milligram per square meter (mg/m\^2) + Cisplatin (70 mg/m\^2) or Carboplatin (Area under the concentration-time curve \[AUC\] 4.5) followed by Avelumab (800 mg)

Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Avelumab

Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy

EXPERIMENTAL

Trilaciclib (240 mg/m\^2) + Gemcitabine (1000 mg/m\^2) + Cisplatin (70 mg/m\^2) or Carboplatin (AUC 4.5) followed by Trilaciclib (240 mg/m\^2) + Avelumab (800 mg)

Drug: Trilaciclib; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Avelumab

Interventions

Trilaciclib DRUG

Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered.

Also known as: Cosela, G1T28

Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy

Gemcitabine DRUG

Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle

Platinum-based chemotherapy followed by avelumab maintenance therapy; Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy

Cisplatin DRUG

Cisplatin administered IV on Day 1 of each 21-day cycle

Platinum-based chemotherapy followed by avelumab maintenance therapy; Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy

Carboplatin DRUG

Carboplatin administered IV on Day 1 of each 21-day cycle

Platinum-based chemotherapy followed by avelumab maintenance therapy; Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy

Avelumab DRUG

Avelumab administered IV on Day 1 of each 14-day maintenance cycle

Also known as: Bavencio

Platinum-based chemotherapy followed by avelumab maintenance therapy; Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy

Eligibility Criteria

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

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.

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)

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (34)

Valkyrie Clinical Trial

Los Angeles, California, 90067, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Rocky Mountain Cancer Centers

Littleton, Colorado, 80120, United States

Location

Florida Cancer Specialists - South

Fort Myers, Florida, 33901, United States

Location

Woodlands Medical Specialists

Pensacola, Florida, 32503, United States

Location

Florida Cancer Specialists - North

St. Petersburg, Florida, 33705, United States

Location

Beacon Cancer Center PLLC

Coeur d'Alene, Idaho, 83814, United States

Location

The Harry and Jeanette Weinberg Cancer Institute

Baltimore, Maryland, 21237, United States

Location

New York Oncology Hematology, P.C.

Albany, New York, 12206, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Northwest Cancer Specialists, P.C.

Tigard, Oregon, 46241, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie

Strasbourg, Bas-Rhin, 67091, France

Location

Institut Bergonié - Oncologie Médicale et Pédiatrique

Bordeaux, Gironde, 33076, France

Location

Centre Léon Bérard - Département d'oncologie médicale

Lyon, 69373, France

Location

Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale

Paris, 75015, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

High Technology Hospital MedCenter LTD

Batumi, Adjara, 6010, Georgia

Location

National Center of Urology Named after Laur Managadze

Tbilisi, 0144, Georgia

Location

LTD "Multiprofile Clinic Consilium Medulla"

Tbilisi, 186, Georgia

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint

Szolnok, Jász-Nagykun-Szolnok, H-5000, Hungary

Location

Országos Onkológiai Intézet

Budapest, 1122, Hungary

Location

Uzsoki Utcai Kórház

Budapest, H-1145, Hungary

Location

Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

ALTHAIA, Xarxa Assistencial Universitiria de Manresa

Manresa, Barcelona, 08243, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Vall d´Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona - Servicio de Oncología Médica

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

H.U. V. de las Nieves

Granada, 18014, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Politecnic Universitari La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

trilaciclib; Gemcitabine; Cisplatin; Carboplatin; avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Limitations and Caveats

This study was terminated earlier than initially proposed by the Sponsor for non-safety related reasons.

Results Point of Contact

• Title: Clinical Trial Info.
• Organization: G1 Therapeutics, Inc.

clinicalinfo@g1therapeutics.com

919-213-9835

Study Officials

• Clinical study director

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Random assignment (1:1) to one of two treatment arms

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 14, 2021
• Study Start: June 4, 2021
• Primary Completion: April 7, 2023
• Study Completion: March 1, 2024
• Last Updated: September 8, 2025
• Results First Posted: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); HU (3); GE (3); US (13); ES (10)