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

NCT04430036 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CTMS 19-0193HSC20200027H
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Urinary Bladder Neoplasms

Keywords

muscle-invasive, non-metastatic

Outcome Measures

Primary Outcomes (1)

• Pathologic Tumor Downstaging of >T2 to pT0

  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.

  Completion of four 21 day cycles (approximately 10 weeks)

Secondary Outcomes (4)

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

  Baseline to 90 days

• Pathologic Downstaging to <T2 Rate

  Baseline to Completion of four 21 day cycles (approximately 10 weeks)

• Completion of Surgery

  90 days

• Progression-free Survival at 1 Year

  1 year

Other Outcomes (1)

• Correlate Immune Outcomes

  2 years

Study Arms (1)

Cisplatin, Gemcitabine plus human monoclonal antibodies

EXPERIMENTAL

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.

Drug: AGEN1884; Drug: AGEN2034; Drug: Cisplatin; Drug: Gemcitabine

Interventions

AGEN1884 DRUG

A fully human monoclonal Anti-PD-1 Antibody

Also known as: anti-CTLA-4 antibody

Cisplatin, Gemcitabine plus human monoclonal antibodies

AGEN2034 DRUG

A fully human monoclonal Anti-PD-1 Antibody

Also known as: Anti-PD-1

Cisplatin, Gemcitabine plus human monoclonal antibodies

Cisplatin DRUG

Alkylating antineoplastic agent

Also known as: Gemzar, Platinol® and Platinol®-AQ

Cisplatin, Gemcitabine plus human monoclonal antibodies

Gemcitabine DRUG

Antimetabolite antineoplastic agent

Also known as: Gebina, Gemalata, Gembin, Gembine, Gembio, Gemcel, Gemcetin

Cisplatin, Gemcitabine plus human monoclonal antibodies

Eligibility Criteria

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

You may qualify if:

• Diagnosis of muscle-invasive, non-metastatic urothelial carcinoma of the bladder, cT2-4, N0-1, M0
• Eligible to receive cisplatin-based chemotherapy, with eligibility defined as meeting all of the following criteria:
• Eastern Cooperative Oncology Group performance status of ¬0-1
• Creatinine clearance (CrCl) of \>50 mL/min, as measured by 24-hour urine collection or estimated by the CKD-EPI equation. Patients with CrCl between 50 - 60 mL/min are eligible for the study but will receive split dose cisplatin
• Grade \< 2 hearing loss
• Grade \< 2 peripheral neuropathy
• New York Heart Association Class \< III heart failure
• Eligible to receive gemcitabine as dosed here
• Patients must have organ and marrow function meeting the criteria below:
• Absolute neutrophil count \> 2,000/mcL Hemoglobin \> 9.0 mg/mL Platelets \> 100,000/mcL Total bilirubin within normal limits or known to be elevated due to a benign conjugation defect such as Gilbert's syndrome, as evidenced by normal conjugated bilirubin level AST/ALT \< 3X institutional normal limits Creatinine clearance (CrCl) \> 50 mL/min/1.73m2, as measured with 24 hr urine collection or estimated by CKD-EPI, whichever is greater
• Signed, written informed consents to allow transfer of tumor tissue and production of peptides and to receive experimental treatment and monitoring if agreeable, or monitoring without experimental treatment otherwise
• Age ≥18 years
• Available fresh tissue from surgical excision. If fresh tissue is not available, archival tissue may be used.
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential (other than by medical reasons) is defined as 1 of the following:
• ≥ 45 years of age and amenorrheic for \>1 year by self-report.

You may not qualify if:

• Subjects must not have previously received a checkpoint inhibitor ie, anti-PD-1, anti-PD L1, or anti CTLA-4 antibody.
• Subjects must not have previously received anticancer medications or investigational drugs for the disease under study within the following windows:
• a. ≤ 28 days for prior monoclonal antibody used for anticancer therapy, with the exception of denosumab b. ≤ 7 days for immunosuppressive treatment for any reason, with the following exceptions: i. Physiologic steroid replacement for adrenal insufficiency (e.g., \<10 mg prednisone per day) is permitted.
• ii. Use of inhaled or topical corticosteroid for radiographic procedures is permitted.
• c. Systemic corticosteroids \< 7 days are not allowed except as defined above. d. ≤ 28 days before first dose of study drug for all other investigational study drugs or devices
• Has persisting toxicity related to prior therapy of National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE) Grade \>1 severity.
• Note: Sensory neuropathy or alopecia of Grade ≤2 is acceptable.
• Has known severe hypersensitivity reactions to fully human monoclonal antibodies (NCI-CTCAE Version 5.0 Grade ≥3), any history of anaphylaxis, or uncontrolled asthma.
• Active or history of any autoimmune disease (subjects with diabetes type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible). Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus or autoimmune vasculitis \[e.g., Wegener's Granulomatosis\] are excluded from this study.
• Any condition requiring systemic treatment with corticosteroids (\>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroids doses \>10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Uncontrolled intercurrent illness, including but not limited to uncontrolled infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or social situations that would limit compliance with study requirements in the opinion of the treating investigator or medical monitor.
• History of intolerance or allergic reactions attributed to compounds of similar chemical or biologic composition to AGEN1884 or AGEN2034.
• Women who are pregnant or breastfeeding.
• Receipt of a live vaccine within 30 days prior to the first dose of study drug.
• Inability to adhere to the protocol

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

balstilimab; spartalizumab; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Robert Svatek, MD
• Organization: University of Texas Health Science Center at San Antonio

svatek@uthscsa.edu

210-567-5643

Study Officials

• Chethan Ramamurthy, MD

  University of Texas Health Science Center San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: June 12, 2020
• Study Start: October 14, 2020
• Primary Completion: October 18, 2021
• Study Completion: March 14, 2022
• Last Updated: April 4, 2024
• Results First Posted: April 4, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)