Clinical trial NCT05315700: Study of ORIC-114 in Patients with Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Official title: An Open-Label, Phase 1/2 Study of ORIC-114 As a Single Agent or in Combination with Chemotherapy, in Patients with Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Keywords: EGFR exon 20 insertion mutation
Atypical EGFR mutation
HER2 exon 20 insertion mutation
HER2 amplification/overexpression
NSCLC
Breast cancer
Lead sponsor: ORIC Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-04-07
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Interval 3+3 dose escalation design
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish the recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of ORIC-114 as a Single Agent or in Combination with Chemotherapy when administered to patients with advanced solid tumors harboring an EGFR or HER2 alteration.

Detailed description: ORIC-114 is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR and HER2 alterations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.

This is a first-in-human, open-label, single arm, multicenter, dose escalation study of ORIC-114 as a single agent (Part I), followed by dose optimization (Part II) to establish the recommended phase 2 dose (RP2D) and antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options. After the optimal RP2D has been determined, Phase 2 will be initiated via protocol amendment to add one or more expansion cohorts of patients with specific tumor types, treatment history, and/or expression of a specific biomarker to evaluate the antitumor activity of ORIC-114.

After completion of Part I dose escalation, Part III, a dose escalation study of ORIC-114 in combination with chemotherapy (carboplatin-pemetrexed) may be initiated to establish the RP2D and/or MTD and antitumor activity for the combination (US sites only).

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented EGFR or HER2 exon 20 insertion mutation or atypical EGFR mutation as determined by any nucleic acid-based diagnostic testing method, or HER2 amplification/overexpression as determined by an immunohistochemistry (IHC) or an in situ hybridization (ISH) test

  1. Part I Dose Escalation (CLOSED) Any solid tumor with

     * EGFR exon 20 insertion mutation
     * HER2 exon 20 insertion mutation
     * Atypical EGFR mutations (NSCLC only) (Appendix 8)
     * HER2 amplification or overexpression (HER2+)
     * Previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
  2. Part I Extension (ONGOING)

     * Cohort IA: Patients with HER2+ breast cancer previously received and progressed on or after available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable
     * Cohort IB: NSCLC patients with EGFR exon 20 insertion mutation previously treated with chemotherapy and amivantamab
     * Cohort IC: Treatment-naïve NSCLC patients with EGFR exon 20 insertion mutation
  3. Part II Dose Optimization (ONGOING): NSCLC patients with

     * Cohort IIA: EGFR exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to an EGFR exon 20 targeted agent, ie, must have declined or be ineligible for all available exon 20 targeted therapies with proven benefit
     * Cohort IIB: HER2 exon 20 insertion mutation, patients must have received platinum-based chemotherapy or other chemotherapy regimen if platinum- based chemotherapy was contraindicated. Additionally, patients must be naïve to a HER2 exon 20 targeted TKI
     * Cohort IIC: Atypical EGFR mutation, patients may have received a prior EGFR TKI
* Agreement and ability to undergo pretreatment biopsy
* Measurable disease according to RECIST 1.1
* CNS involvement, which is either previously treated and controlled, or untreated and asymptomatic
* ECOG performance status of 0 or 1
* Adequate organ function

Exclusion Criteria:

* Known EGFR T790M mutation
* Leptomeningeal disease and spinal cord compression

  -- Except if LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator; the subject must be free of neurological symptoms of LMD
* History of class III or IV congestive heart failure or severe non-ischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months
* Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
* Known, symptomatic human immunodeficiency virus (HIV) infection
* Known active infection requiring treatment or history of hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients positive for HBsAg but normal HBV DNA level are allowed.
* Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes
* Any other concurrent serious uncontrolled medical, psychological, or addictive conditions

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: 12 months
measure: Maximum plasma concentration (Cmax)
timeFrame: 28 Days
measure: Time of maximum observed concentration (Tmax)
timeFrame: 28 Days
measure: Area under the curve (AUC)
timeFrame: 28 Days
measure: Apparent plasma terminal elimination half-life (t1/2)
timeFrame: 28 Days
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 36 months
measure: Duration of response (DOR)
timeFrame: 36 months
measure: Clinical benefit rate (CBR)
timeFrame: 36 months
measure: Progression-free survival (PFS)
timeFrame: 36 months
measure: Intracranial response rate (CR and/or PR)
timeFrame: 36 months
measure: Intracranial progression-free survival (PFS)
timeFrame: 36 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Huntington Beach
country: United States
facility: City of Hope
state: California
city: Irvine
country: United States
facility: City of Hope
state: California
city: Long Beach
country: United States
facility: City of Hope
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: NYU Langone Health Perlmutter Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare System
state: South Carolina
city: Fairfax
country: United States
facility: Next Oncology
state: Virginia
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Nedlands
country: Australia
facility: One Clinical Research, Hollywood Medical Centre
city: Sydney
country: Australia
facility: Sydney Adventist Health
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Shatin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Catholic University of Korea, St, Vincent Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Gdańsk
country: Poland
facility: Medical University of Gdańsk
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
Study officials:
affiliation: ORIC Pharmaceuticals
name: Pratik S. Multani, MD, MS
role: STUDY_DIRECTOR
References: