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

Brief Title

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

Official Title

A Phase 2, Randomized, Open-Label Study of Trilaciclib Administered With First-Line Platinum-Based Chemotherapy and Avelumab Maintenance Therapy in Patients With Untreated, Locally Advanced or Metastatic Urothelial Carcinoma (PRESERVE 3)

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 patients receiving first-line treatment for
      advanced/metastatic bladder cancer.
    

Detailed Description

      Patients will be randomly assigned (1:1) to receive standard of care platinum-based
      chemotherapy (with or without the addition of trilaciclib) administered intravenously (IV) in
      21-day cycles followed by standard of care avelumab maintenance therapy (with or without the
      addition of trilaciclib) administered IV in 14-day cycles.

      Patients enrolled in the study will be eligible to receive 4-6 cycles of platinum-based
      chemotherapy, and patients without progressive disease (PD) as per Response Evaluation
      Criteria in Solid Tumors (RECIST) v1.1 guidelines (i.e., with an ongoing complete response
      [CR], partial response [PR], or stable disease) after platinum-based chemotherapy will be
      eligible to receive avelumab maintenance therapy until disease progression, unacceptable
      toxicity, withdrawal of consent, Investigator decision, or the end of the trial, whichever
      comes first.

      Patients will be followed for survival approximately every 3 months after receiving the last
      dose of study medication.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Progression-Free Survival

Secondary Outcome

 Anti-tumor Effects

Condition

Urothelial Carcinoma

Intervention

Trilaciclib

Study Arms / Comparison Groups

 Platinum-based chemotherapy followed by avelumab maintenance therapy

Description:  Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

92

Start Date

June 4, 2021

Completion Date

May 2024

Primary Completion Date

March 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥18 years

          2. Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or
             metastatic urothelial carcinoma (M1, Stage IV)

          3. Measurable disease as defined by RECIST v1.1

          4. No prior systemic therapy in the inoperable, locally advanced, or metastatic setting
             including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or
             investigational agents

          5. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless
             approved by the Medical Monitor

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          7. Adequate organ function as demonstrated by normal laboratory values

        Exclusion Criteria:

          1. Prior treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, 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

          2. Malignancies other than urothelial carcinoma within 3 years prior to randomization,
             except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in
             situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on
             surveillance without any plans for treatment intervention (e.g., surgery, radiation,
             or castration)

          3. Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring
             immediate treatment with radiation therapy or steroids.

          4. QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec

          5. Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin

          6. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any
             history of anaphylaxis, or uncontrolled asthma

          7. Prior hematopoietic stem cell or bone marrow transplantation, or solid organ
             transplantation

          8. Pregnant or lactating women

          9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
             agent

         10. Current use of immunosuppressive medication, EXCEPT for the following:

               1. Intranasal, inhaled, topical steroids, or local steroid injection (e.g.,
                  intra-articular injection)

               2. Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or
                  equivalent

               3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication)
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Clinical Contact, , 

Location Countries

France

Location Countries

France

NCT ID

NCT04887831

Organization ID

G1T28-209

Responsible Party

Sponsor

Study Sponsor

G1 Therapeutics, Inc.

Study Sponsor

Clinical Contact, Study Director, G1 Therapeutics, Inc.

Verification Date

January 2023