A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors
- Conditions
- Solid TumorsAdvanced Solid TumorsMetastatic Solid Tumors
- Interventions
- Registration Number
- NCT05836324
- Lead Sponsor
- Incyte Corporation
- Brief Summary
To evaluate the safety, tolerability, and DLTs and determine the MTD and/or RDE(s) of INCA33890 in participants with select advanced or metastatic solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 408
- ≥18 years old
- Histologically or cytologically confirmed advanced or metastatic malignancies as defined in the protocol.
- Part 1: Participants must have experienced disease progression after treatment with, be intolerant to, or be ineligible for, or refused available therapies, including anti-PD-(L)1 or anti-CTLA4 therapy if applicable, that are known to confer clinical benefit. Part 2: depending on cohort, participants may have received or not prior treatment for the malignancy under study.
- ECOG performance status score of 0 or 1.
- Willingness to undergo pre- and on-treatment tumor biopsy (core or excisional). Biopsies are mandatory depending on the cohorts.
- Presence of measurable disease according to RECIST v1.1.
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Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years.
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Not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy.
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Has active autoimmune disease requiring systemic immunosuppression with corticosteroids.
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Brain or CNS metastases untreated or that have progressed.
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History of organ transplant, including allogeneic stem cell transplantation.
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History of clinically significant or uncontrolled cardiac disease.
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Active HBV, active HCV, or HIV positive.
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Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent).
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Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
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Participants that have been initiated on or had modifications in anticoagulation therapies within the last 3 months prior to first dose of treatment.
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Significant concurrent, uncontrolled medical condition, eg:
- Cardiovascular: Participants with known vasculitis, aneurisms, and other vascular malformations of clinical significance or history of myocarditis.
- Gastrointestinal: Any bowel obstruction within 60 days prior to C1D1.
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Participants with adequate laboratory values within the protocol defined ranges.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1a - Dose Escalation Monotherapy INCA33890 INCA33890 will be administered at the protocol-defined dose based on cohort assignment. Part 1b-Dose Expansion Monotherapy INCA33890 INCA33890 will be administered at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 1 bevacizumab INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 1 INCA33890 INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 2 INCA33890 INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 2 bevacizumab INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 2 FOLFIRI INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 3 INCA33890 INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 3 bevacizumab INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 3 FOLFOX INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 2 bevacizumab INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 4 INCA33890 INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 1 bevacizumab INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 3 bevacizumab INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 4 INCA33890 INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment. Part 2a - Dose Escalation Combination Therapy - Group 4 Cetuximab INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 2 FOLFIRI INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 1 INCA33890 INCA33890 will be administered in combination with bevacizumab at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 2 INCA33890 INCA33890 will be administered in combination with bevacizumab and FOLFIRI at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 3 INCA33890 INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 3 FOLFOX INCA33890 will be administered in combination with bevacizumab and FOLFOX at the protocol-defined dose based on cohort assignment. Part 2b - Dose Expansion Combination Therapy - Group 4 Cetuximab INCA33890 will be administered in combination with cetuximab at the protocol-defined dose based on cohort assignment.
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicities (DLTs) Up to 28 days Treatment Emerging Adverse Events (TEAEs) Up to 2 years TEAEs leading to dose modification or discontinuation Up to 2 years
- Secondary Outcome Measures
Name Time Method Objective response Rate 2 years Disease Control Rate 2 years Duration of Response 2 years Pharmacokinetics Parameter : Cmax of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up Pharmacokinetics Parameter : AUC(0-t) of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up Pharmacokinetics Parameter : AUC 0-∞ of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up Pharmacokinetics Parameter : Tmax of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up Pharmacokinetics Parameter : Cmin of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up Pharmacokinetics Parameter : CL of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up Pharmacokinetics Parameter : Vz of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up Pharmacokinetics Parameter : t1/2 of INCA33890 Pre dose - Day 1 of Cycle 1(C1D1)- 28 (each cycle is 28 days), Day 15 of Cycle 1-3; 10min and 4hrs Post dose(PD) - C1D1,C1D4, 24hrs PD C1D2, any time PD Day 4, 8, 22, of Cycle 1, and any time during 30 day Follow Up
Trial Locations
- Locations (34)
Centro Ricerche Cliniche Di Verona
🇮🇹Verona, Italy
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Cancer and Hematology Centers of Western Michigan-Start Midwest
🇺🇸Grand Rapids, Michigan, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Lifespan Cancer Research Institute
🇺🇸Providence, Rhode Island, United States
University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States
Rigshospitalet Uni of Hospital of Copenhagen
🇩🇰Copenhagen, Denmark
Herlev Og Gentofte Hospital
🇩🇰Herlev, Denmark
Odense University Hospital
🇩🇰Odense C, Denmark
Vejle Hospital
🇩🇰Vejle, Denmark
Centre Leon Berard
🇫🇷Lyon, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
Fondazione Irccs Istituto Nazionale Dei Tumori
🇮🇹Milano, Italy
Irccs Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Kansai Medical University Hospital
🇯🇵Hirakata, Japan
The Cancer Institute Hospital of Jfcr
🇯🇵Koto-ku, Japan
Start Barcelona
🇪🇸Barcelona, Spain
Hospital General Universitario Vall D Hebron
🇪🇸Barcelona, Spain
Fundacion Jimenez Diaz University Hospital
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Istituto Oncologico Della Svizzera Italiana
🇨🇭Bellinzona, Switzerland
Centre Hospitalier Universitaire Vaudois (Chuv)
🇨🇭Lausanne, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
Cambridge University Hospitals Nhs Foundation Trust
🇬🇧Cambridge, United Kingdom
Guys and St Thomas Nhs Foundation Trust
🇬🇧London, United Kingdom
Imperial College Healthcare Nhs Trust - Hammersmith Hospital
🇬🇧London, United Kingdom
The Christie Nhs Foundation Trust Uk
🇬🇧Manchester, United Kingdom
Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust
🇬🇧Newcastle Upon Tyne, United Kingdom