Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Antibodies

Antibodies, Monoclonal

Cisplatin

Immunoglobulins

Antimetabolites

Antineoplastic Agents, Alkylating

The safety run-in of the study will first enroll three patients who will begin treatment with cisplatin and gemcitabine plus AGEN2034 and AGEN1884 as outlined in the treatment plan. These first 3 patients will be assessed for DLTs and there will be a pause in enrollment until all three complete the DLT period. If there are no DLTs in the first 3 patients, we will proceed to further accrual to stage I of phase II. If there is 1 DLT in the initial 3 patients, we will enroll 3 additional patients to the safety run-in. If \> 2 DLTs are experienced in the initial 3 patients, the study will be terminated, otherwise additional subjects will be enrolled into the phase ll first stage and reassessed after 2 cycles of therapy and proceed to planned surgery. If criteria are met to continue to the second stage of the Phase II portion of the study, additional patients will be enrolled for an anticipated total of 36 evaluable patients. Patients will be treated and endpoints evaluated.

A fully human monoclonal Anti-PD-1 Antibody

AGEN1884

AGEN2034

Chethan Ramamurthy, MD

This is a phase II trial to evaluate the tolerability, efficacy, and immune outcomes of AGEN1884 plus AGEN2034 concurrent with cisplatin and gemcitabine in the neoadjuvant treatment of muscle-invasive, non-metastatic bladder cancer prior to radical cystectomy.

We will begin with an initial safety run-in to establish the safety of the combination prior to expansion to the full planned phase II. The overall phase II will be an open-label, single arm study in two stages to evaluate the efficacy of the combination in pathologic downstaging of MIBC. Patients will receive four 21-day cycles of neoadjuvant therapy consisting of cisplatin and gemcitabine plus AGEN2034 in all 4 cycles and AGEN1884 in cycles 1 and 3. Patients will proceed to radical cystectomy within 10 weeks after the final dose of this therapy. The primary endpoint of pathologic tumor downstaging will be assessed at the time of cystectomy.

This is a phase II trial to evaluate the tolerability, efficacy, and immune outcomes of AGEN1884 plus AGEN2034 concurrent with cisplatin and gemcitabine in the neoadjuvant treatment of muscle-invasive, non-metastatic bladder cancer prior to radical cystectomy. We will begin with an initial safety run-in to establish the safety of the combination prior to expansion to the full planned phase II. The overall phase II will be an open-label, single arm study in two stages to evaluate the efficacy of the combination in pathologic downstaging of MIBC.

AGEN1884 Plus AGEN2034 Combined With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer

A Phase II Trial of Neoadjuvant AGEN1884 Plus AGEN2034 in Combination With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer Prior to Radical Cystectomy

To correlate clinical outcomes with immune and biologic endpoints and identify patient and tumor characteristics that can predict treatment responses

pT0 or pCR (defined as no residual tumor in bladder and lymph nodes on resected specimen). Surgery should be performed within 6 weeks after completing up to 4 cycles (last dose) of neoadjuvant therapy, but can be done up to 10 weeks after treatment ends to be evaluable. Otherwise this patient must be replaced for response evaluation.

Evaluation of safety and tolerability of using Agen1884 plus AGEN2034 plus cisplating and gemcitabine chemotherapy in the neoadjuvant treatment of muscle-invasive bladder cancer prior to radial cystectomy. Number of adverse events assessed between 3-5 using the National Cancer Institution Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)

Number of subjects who achieved downstaging of the tumor at completion of the possible 4 chemotherapy cycles.

Number of subjects that progressed from therapy to surgery

Number of subjects that survived to 1 year from study start without disease progression

The University of Texas Health Science Center at San Antonio

Treatment with the following drugs:

AGEN1884: A fully human monoclonal Anti-PD-1 Antibody

AGEN2034: A fully human monoclonal Anti-PD-1 Antibody

Cisplatin: Alkylating antineoplastic agent

Gemcitabine: Antimetabolite antineoplastic agent

Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies

Participants enrolled with muscle-invasive bladder cancer.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Robert Svatek, MD

Pathologic Tumor Downstaging of >T2 to pT0

Evaluation of Safety and Tolerability of AGEN1884 Plus AGEN2034 Plus Cisplatin and Gemcitabine

Pathologic Downstaging to <T2 Rate

Completion of Surgery

Due to early termination of the study, data were not collected for this outcome measure

Progression-free Survival at 1 Year

Due to early termination, not data were collected for this outcome

Correlate Immune Outcomes

Patients will be treated and endpoints evaluated:

AGEN1884: A fully human monoclonal Anti-PD-1 Antibody AGEN2034: A fully human monoclonal Anti-PD-1 Antibody Cisplatin: Alkylating antineoplastic agent Gemcitabine: Antimetabolite antineoplastic agent

Spots Global Cancer Trial Database for AGEN1884 Plus AGEN2034 Combined With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial