An Umbrella Study to Determine the Safety and Efficacy of Various Monotherapy or Combination Therapies in Neoadjuvant Urothelial Carcinoma (Optimus)

• ClinicalTrials.gov Identifier: NCT04586244
• Recruitment Status: Recruiting
• First Posted: October 14, 2020
• Last Update Posted: December 5, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Study Description

Brief Summary:

This is a multicenter, open-label, randomized, Phase 2 umbrella study of various neoadjuvant treatment combinations in participants who have muscle-invasive urothelial carcinoma of the bladder and are cisplatin-ineligible or refusing cisplatin therapy and awaiting radical cystectomy.

Condition or disease	Intervention/treatment	Phase
Urothelial Carcinoma	Drug: retifanlimab; Drug: epacadostat; Drug: INCAGN02385; Drug: INCAGN02390	Phase 2

Detailed Description:

Participants will be stratified based on Programmed cell Death-Ligand 1 (PD-L1) Combined Positive Score ( CPS) < 10 and PD-L1 CPS ≥ 10.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open Label
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized, Phase 2, Umbrella Study to Investigate the Biological Rational of Various Neoadjuvant Therapies for Participants With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Cisplatin-Ineligible or Refuse Cisplatin Therapy and Undergoing Radical Cystectomy
• Actual Study Start Date: January 14, 2022
• Estimated Primary Completion Date: April 30, 2024
• Estimated Study Completion Date: June 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Group A; epacadostat will be administered in combination with retifanlimab.	Drug: retifanlimab; retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,; Drug: epacadostat; epacadostat will be administered daily twice daily orally up to and including day of surgery.
Experimental: Treatment Group B; retifanlimab will be administered as monotherapy.	Drug: retifanlimab; retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,
Experimental: Treatment Group C; epacadostat will be administered as monotherapy.	Drug: epacadostat; epacadostat will be administered daily twice daily orally up to and including day of surgery.
Experimental: Treatment Group D; retifanlimab will be administered in combination with INCAGN02385.	Drug: retifanlimab; retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,; Drug: INCAGN02385; INCAGN02385 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.
Experimental: Treatment Group E; retifanlimab will be administered in combination with INCAGN02385 and INCAGN02390.	Drug: retifanlimab; retifanlimab will be administered via IV over 30 minutes (+ 15 min) on Day 1 of each 28-day cycle, up to 3 cycles,; Drug: INCAGN02385; INCAGN02385 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.; Drug: INCAGN02390; INCAGN02390 will be administered via IV over 30 minutes (-5/+10 min) every 2 weeks.

Outcome Measures

Primary Outcome Measures :

1. Immunologic intratumoral changes [ Time Frame: up to 3 months ]
   Defined as change from baseline in CD8+ lymphocytes within resected tumor

Secondary Outcome Measures :

1. Number of Treatment Emergent Adverse Events (TEAE) [ Time Frame: up to 6 months ]
   Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 30 days after last dose of study drug.
2. pathological complete response [ Time Frame: up to 3 months ]
   Defined as percentage of participants with absence of tumor as well as no observed tumor in the nodes post neoadjuvant therapy and pre-surgery.
3. Major pathological response [ Time Frame: up to 3 months ]
   Defined as absence of tumor cells determined pre- surgery or in-Situ absence of tumor cells in the nodes and no metastases.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically confirmed transitional cell urothelial carcinoma. Participants with mixed histologies are required to have a dominant (ie, 50% at least) transitional cell pattern.
• Clinical stage T2-T3b, N0, M0 muscle invasive urothelial carcinoma by CT (or MRI) (Stage II-IIIA per AJCC 2018)
• Refuse cisplatin therapy (does not apply in France) or are ineligible for cisplatin therapy per modified Galsky criteria with exclusion of Eastern Cooperative Oncology Group( ECOG) PS 2 participants
• Eligible for radical cystectomy
• Eastern Cooperative Oncology Group (ECOG) Performance Status( PS) 0 or 1.
• Pretreatment tumor biopsy must be a tumor block or 20 unstained slides from biopsy of primary tumor containing at least 20% tumor.
• Willingness to avoid pregnancy or fathering children from screening through 100 days in the US and 190 days in Europe after the last dose of study drug

Exclusion Criteria:

• Participation in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) before first dose.
• Previously received systemic therapy for bladder cancer or received prior treatment with checkpoint inhibitor agents (such as anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4).
• Evidence of measurable nodal or metastatic disease.
• Concurrent anticancer therapy.
• Has had major surgery within 4 weeks before enrollment (C1D1).
• Has had known additional malignancy other than muscle-invasive Urothelial Bladder Cancer ( miUBC) that is progressing or requires active treatment, along with some protocol exceptions, or history of other malignancy within 2 years of study entry, with some predefined-protocol exceptions.
• Has active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg daily doses of prednisone or equivalent) or immunosuppressive drugs within 2 years of Day 1 of study treatment.
• Participants with laboratory values outside of protocol defined ranges.
• Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent).
• Has a known active hepatitis B (defined as HBsAg and total anti-HBc positive results) or hepatitis C (HCV Ab positive result and HCV RNA >LLoD) or HIV,HBV, HCV or hepatitis virus coinfection.
• Participants with HIV+ disease along with protocol defined exceptions that don't have undetectable viral load along with other protocol exceptions.
• Has known carcinomatous meningitis.
• Active infection requiring systemic antibiotics ≤ 14 days from first dose of study drug.
• Participants with known or suspected active COVID-19 infection.
• Use of probiotics within 28 days from first dose of study drug.
• Current use of prohibited medication as per protocol.
• Has not recovered to ≤ Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention.
• History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 450 milliseconds is excluded.
• History of a gastrointestinal condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) that may affect oral drug absorption.
• Has received a live vaccine within 30days of planned start of study therapy
• Participants with impaired cardiac function or clinically significant cardiac disease
• Prior allogenic tissue/solid organ transplant
• Evidence of interstitial lung disease or active, noninfectious pneumonitis.
• Has known hypersensitivity to any of the study drugs, excipients, including mannitol or another monoclonal antibody which cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
• Any ≥ Grade 2 immune-related toxicity while receiving prior immunotherapy.
• History of serotonin syndrome after receiving 1 or more serotonergic drugs.
• Concomitant use of medications that are known to be substrates of CYP1A2, CYP2C8, or CYP2C19 with narrow therapeutic window are prohibited (see Section 6.6.3).
• Patients who are receiving or required to receive medications that are known to be UGT1A9 inhibitors (see Section 6.6.3).

Contacts and Locations

Contacts

Contact: Incyte Corporation Call Center (US); 1.855.463.3463; medinfo@incyte.com

Contact: Incyte Corporation Call Center (ex-US); +800 00027423; eumedinfo@incyte.com

Locations

United States, Iowa

University of Iowa; Recruiting

Iowa City, Iowa, United States, 52242

United States, Ohio

University of Cincinnati; Completed

Cincinnati, Ohio, United States, 45267

Ohio State University Medical Center Division of H; Not yet recruiting

Columbus, Ohio, United States, 43210

United States, Oregon

Oregon Health & Science University; Recruiting

Portland, Oregon, United States, 97239-4501

France

Hospital Saint Louis; Recruiting

Paris Cedex 10, France, 75475

Hopital Europeen Georges Pompidou (Hegp); Recruiting

Paris Cedex 15, France, 75015

Institut Gustave Roussy; Recruiting

Villejuif Cedex, France, 94805

Italy

Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari; Recruiting

Bari, Italy, 70124

L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI; Recruiting

Bologna, Italy, 40138

Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele; Recruiting

Milano, Italy, 20132

Universita Campus Bio Medico Di Roma; Not yet recruiting

Roma, Italy, 00128

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma); Recruiting

Verona, Italy, 37124

Sponsors and Collaborators

Incyte Corporation

Investigators

• Study Director: Diane Hershock, MD; Incyte Corporation

More Information

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT04586244
• Other Study ID Numbers: INCB 24360-901
• First Posted: October 14, 2020
• Last Update Posted: December 5, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• URL: https://www.incyte.com/our-company/compliance-and-transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation:

Muscle-invasive cisplatin-ineligible; urothelial carcinoma of the bladder; radical cystectomy.; epacadostat; retifanlimab; TIM-3; LAG-3

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Transitional Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms