A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
- Conditions
- Solid Tumors
- Interventions
- Registration Number
- NCT06179160
- Lead Sponsor
- Incyte Corporation
- Brief Summary
This study is conducted to determine the safety and tolerability of INCB161734 as a single agent or in combination with other anticancer therapies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 466
-
≥18 years old
-
Locally-advanced or metastatic solid tumor with KRAS G12D mutation
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For Part 1 and Part 2 Combination Groups 1 and 2: Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment to improve the disease outcome
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For Part 2 Combination Groups 3 and 4: No more than 1 prior standard treatment
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Cohort specific requirements as follows:
-
Parts 1A and 1D: Histologically or cytologically confirmed malignant solid tumor of any tissue origin
-
Part 1B
- Disease group 1: diagnosis of PDAC and ≤ 2 prior standard systemic regimens for pancreatic cancer
- Disease group 2: diagnosis of CRC
- Disease group 3: diagnosis of NSCLC
- Disease group 4: diagnosis of other advanced solid tumor and not part of Disease groups 1, 2 or 3
-
Part 1c: Confirmed diagnosis of PDAC, CRC, or NSCLC
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Parts 2A and 2B
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Combination 1: Diagnosis of PDAC or Diagnosis of CRC and
- Prior treatment in the advanced setting with a fluoropyrimidine-based chemotherapy regimen containing either oxaliplatin or irinotecan and
- In Part 2a: ≤ 3 prior standard regimens
- In Part 2b: ≤ 2 prior standard regimens
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Combination 2: Diagnoses of PDAC, CRC or NSCLC
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Combination Group 3 (INCB161734 in combination with GEMNabP) and Combination Group 4 (INCB161734 in combination with mFOLFIRINOX):
- Diagnosis of PDAC
- ≤ 1 prior standard systemic regimen for pancreatic cancer
-
-
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Prior treatment with any KRAS G12D inhibitor
- Known additional invasive malignancy within 1 year of the first dose of study drug
- History of organ transplant, including allogeneic stem cell transplantation
- Significant, uncontrolled medical condition
- History or presence of an ECG abnormality
- Inadequate organ function
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 INCB161734 INCB161734 at the protocol-defined dose strength based on cohort assignment. Part 1b: Dose Expansion monotherapy INCB161734 INCB161734 at the protocol-defined dose strength based on cohort assignment. Part 1c: Pharmacodynamic cohort INCB161734 INCB161734 at the protocol-defined dose strength based on cohort assignment. Part 2a: Dose Escalation combination INCB161734 INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2a: Dose Escalation combination Cetuximab INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2a: Dose Escalation combination Retifanlimab INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2a: Dose Escalation combination GEMNabP INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2a: Dose Escalation combination mFOLFIRINOX INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2b: Dose Expansion combination Cetuximab INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2b: Dose Expansion combination Retifanlimab INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2b: Dose Expansion combination GEMNabP INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2b: Dose Expansion combination INCB161734 INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 2b: Dose Expansion combination mFOLFIRINOX INCB161734 in combination at the protocol-defined dose strength based on cohort assignment. Part 1d: Food-Effect INCB161734 Evaluate food effect on drug exposure as defined in the protocol.
- Primary Outcome Measures
Name Time Method Number of participants with Dose Limiting Toxicities (DLTs) Up to 28 days Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Number of participants with TEAEs leading to dose modification or discontinuation Up to 2 years and 90 days Number of participants with TEAEs leading to dose modification or discontinuation.
Number of participants with Treatment-emergent Adverse Events (TEAEs) Up to 2 years and 90 days Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with cetuximab and retifanlimab.
- Secondary Outcome Measures
Name Time Method INCB161734 pharmacokinetic (PK) in Plasma Up to approximately 90 days INCB161734 concentration in plasma.
Duration of Response (DOR) Up to 2 years Defined as the time from earliest date of disease response (Completed Response or Partial Response) until earliest date of disease progression as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or death due to any cause if occurring sooner than progression.
Objective Response Rate (ORR) Up to 2 years Defined as having a best overall Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
Disease Control Response (DCR) Up to 2 years Defined as having a best overall response of CR, PR, or Stable Disease (SD) as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
Related Research Topics
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Trial Locations
- Locations (32)
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Scri Oncology Partners
🇺🇸Nashville, Tennessee, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Stanford University
🇺🇸Palo Alto, California, United States
UCLA Healthcare Hematology-Oncology
🇺🇸Santa Monica, California, United States
Sarah Cannon Research Institue At Healthone
🇺🇸Denver, Colorado, United States
Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Chris Obrien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
St Vincent'S Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Peter Maccallum Cancer Centre
🇦🇺North Melbourne, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
Cliniques Universitaires Ucl Saint-Luc
🇧🇪Brussels, Belgium
Universitair Ziekenhuis Antwerpen (Uza)
🇧🇪Edegem, Belgium
Universitair Ziekenhuis (Uz) Leuven
🇧🇪Leuven, Belgium
The Ottawa Hospital Cancer Center
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Centre Leon Berard
🇫🇷Lyon, France
Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, France
Fondazione Irccs Istituto Nazionale Dei Tumori
🇮🇹Milan, Italy
Irccs Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Centro Ricerche Cliniche Di Verona
🇮🇹Verona, Italy
National Cancer Center Hospital East
🇯🇵Chiba, Japan
The Cancer Institute Hospital of Jfcr
🇯🇵Koto-ku, Japan
Hospital General Universitario Vall D Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Madrid, Spain