Clinical trial NCT06179160: A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
Official title: A Phase 1, Open-Label, Multicenter Study of INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Keywords: INCB161734
KRASG12D Mutation
pancreatic ductal adenocarcinoma (PDAC)
colorectal cancer (CRC)
non-small cell lung cancer (NSCLC)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2023-12-21
Enrollment: 466
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* ≥18 years old
* Locally-advanced or metastatic solid tumor with KRAS G12D mutation
* 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
* For Part 2 Combination Groups 3 and 4: No more than 1 prior standard treatment
* 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
  * Parts 2A and 2B

    * 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
    * Combination 2: Diagnoses of PDAC, CRC or NSCLC
    * 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
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 2 years and 90 days
measure: Number of participants with TEAEs leading to dose modification or discontinuation
timeFrame: Up to 2 years and 90 days
Secondary outcomes:
measure: INCB161734 pharmacokinetic (PK) in Plasma
timeFrame: Up to approximately 90 days
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
measure: Disease Control Response (DCR)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Santa Monica
country: United States
facility: UCLA Healthcare Hematology-Oncology
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institue At Healthone
state: Colorado
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Scri Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: Chris Obrien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent'S Hospital Sydney
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: North Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Brussels
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis (Uz) Leuven
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Lyon
country: France
facility: Centre Leon Berard
city: Toulouse
country: France
facility: Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Milan
country: Italy
facility: Fondazione Irccs Istituto Nazionale Dei Tumori
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Jfcr
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: