Trial Outcomes & Findings for AGEN1884 Plus AGEN2034 Combined With Cisplatin-Gemcitabine for Muscle-Invasive Bladder Cancer (NCT NCT04430036)

NCT ID: NCT04430036

Last Updated: 2024-04-04

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

Completion of four 21 day cycles (approximately 10 weeks)

Results posted on

2024-04-04

Participant Flow

The safety run-in phase will enroll initial subjects who will begin treatment with cisplatin and gemcitabine plus AGEN2034 and AGEN 19884. Dose limiting toxicities will be assessed before beginning Phase ll, Stage 1. Evaluation will occur after 2 cycles of therapy prior to administration of third and fourth cycle therapy and progression to planned surgery. If criteria are met to continue to Stage 2, additional subjects will be enrolled to reach the anticipated total of 36 subjects.

Participant milestones

Participant milestones
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
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
Safety Run in Phase
STARTED
4
Safety Run in Phase
COMPLETED
2
Safety Run in Phase
NOT COMPLETED
2
Phase II, Stage 1
STARTED
0
Phase II, Stage 1
COMPLETED
0
Phase II, Stage 1
NOT COMPLETED
0
Phase ll, Stage 2
STARTED
0
Phase ll, Stage 2
COMPLETED
0
Phase ll, Stage 2
NOT COMPLETED
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
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
Safety Run in Phase
Progression of disease
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
n=4 Participants
Participants enrolled with muscle-invasive bladder cancer.
Age, Continuous
59.75 years
n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
3 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
4 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
4 participants
n=5 Participants

PRIMARY outcome

Timeframe: Completion of four 21 day cycles (approximately 10 weeks)

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.

Outcome measures

Outcome measures
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
n=4 Participants
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
Pathologic Tumor Downstaging of >T2 to pT0
2 Participants

SECONDARY outcome

Timeframe: Baseline to 90 days

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)

Outcome measures

Outcome measures
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
n=4 Participants
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
Evaluation of Safety and Tolerability of AGEN1884 Plus AGEN2034 Plus Cisplatin and Gemcitabine
5 adverse events

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
n=4 Participants
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
Pathologic Downstaging to <T2 Rate
3 Participants

SECONDARY outcome

Timeframe: 90 days

Number of subjects that progressed from therapy to surgery

Outcome measures

Outcome measures
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
n=4 Participants
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
Completion of Surgery
4 Participants

SECONDARY outcome

Timeframe: 1 year

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

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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 years

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

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

Outcome measures

Outcome data not reported

Adverse Events

Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Cisplatin, Gemcitabine Plus Human Monoclonal Antibodies
n=4 participants at risk
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
General disorders
Anorexia
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Musculoskeletal and connective tissue disorders
Arthralgia
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Hepatobiliary disorders
Aspartate aminotransferase increase
25.0%
1/4 • Number of events 3 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Musculoskeletal and connective tissue disorders
Back pain
50.0%
2/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Musculoskeletal and connective tissue disorders
Bone pain
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Gastrointestinal disorders
Diarrhea
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Renal and urinary disorders
Dysuria
50.0%
2/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
General disorders
Fatigue
75.0%
3/4 • Number of events 7 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Gastrointestinal disorders
Gastroesophageal reflux disease
25.0%
1/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
General disorders
Headache
25.0%
1/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Renal and urinary disorders
Hyperkalemia
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
General disorders
Hypertension
25.0%
1/4 • Number of events 3 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Renal and urinary disorders
Hypokalemia
25.0%
1/4 • Number of events 3 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
General disorders
Hypotension
25.0%
1/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Gastrointestinal disorders
Nausea
75.0%
3/4 • Number of events 4 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Blood and lymphatic system disorders
Neutrophil count decreased
50.0%
2/4 • Number of events 5 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
General disorders
Non-cardiac chest pain
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
General disorders
Other
50.0%
2/4 • Number of events 3 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Skin and subcutaneous tissue disorders
Rash maculo-papular
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Vascular disorders
Thromboembolic event
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Infections and infestations
Tooth infection
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Renal and urinary disorders
Urinary frequency
50.0%
2/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Infections and infestations
Urinary tract infection
50.0%
2/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Gastrointestinal disorders
Vomiting
50.0%
2/4 • Number of events 2 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
General disorders
Weight loss
25.0%
1/4 • Number of events 1 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)
Blood and lymphatic system disorders
White blood cells decreased
25.0%
1/4 • Number of events 3 • Baseline to approximately 5 days after last treatment (approximately 10 weeks)

Additional Information

Robert Svatek, MD

University of Texas Health Science Center at San Antonio

Phone: 210-567-5643

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place