Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05315700
• Other study ID #: ORIC-114-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 10, 2022
• Est. completion date: March 2026

Study information

• Verified date: May 2024
• Source: ORIC Pharmaceuticals
• Contact: ORIC Clinical
• Phone: 650-388-5600
• Email: clinical[@]oricpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: March 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• ORIC-114
ORIC-114 oral daily
• Chemotherapy drug
21 days for up to 4 cycles

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown
Australia	Peter MacCallum Cancer Centre	Melbourne
Australia	One Clinical Research, Hollywood Medical Centre	Nedlands
Australia	Sydney Adventist Health	Sydney
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Hong Kong	The Chinese University of Hong Kong	Shatin
Korea, Republic of	Chungbuk University Hospital	Cheongju-si
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Catholic University of Korea, St, Vincent Hospital	Gyeonggi-do
Korea, Republic of	Gachon University Hospital	Incheon
Korea, Republic of	Seoul National Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Medical University of Gdansk	Gdansk
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	The Christie NHS Foundation Trust	Manchester	England
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	Duke Cancer Institute	Durham	North Carolina
United States	Next Oncology	Fairfax	Virginia
United States	City of Hope	Huntington Beach	California
United States	City of Hope	Irvine	California
United States	Mayo Clinic	Jacksonville	Florida
United States	City of Hope	Long Beach	California
United States	Yale Cancer Center	New Haven	Connecticut
United States	NYU Langone Health Perlmutter Cancer Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, San Francisco	San Francisco	California
United States	Spartanburg Regional Healthcare System	Spartanburg	South Carolina
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
ORIC Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hong Kong,  Korea, Republic of,  Poland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase 2 Dose (RP2D)	RP2D as determined by interval 3+3 dose escalation design	12 months
Primary	Maximum plasma concentration (Cmax)	PK of ORIC-114	28 Days
Primary	Time of maximum observed concentration (Tmax)	PK of ORIC-114	28 Days
Primary	Area under the curve (AUC)	PK of ORIC-114	28 Days
Primary	Apparent plasma terminal elimination half-life (t1/2)	PK of ORIC-114	28 Days
Secondary	Objective response rate (ORR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Duration of response (DOR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Clinical benefit rate (CBR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Progression-free survival (PFS)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Intracranial response rate (CR and/or PR)	Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Secondary	Intracranial progression-free survival (PFS)	Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months