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

• Sponsor: ORIC Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05315700
• Collaborator: (none)
• Enrollment: 42
• Locations: 8
• Arm: 1
• Anticipated Duration (Months): 20.7
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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), preliminary antitumor ORIC-114 when administered to patients with advanced solid tumors harboring an EGFR or HER2 alteration .

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor	Drug: ORIC-114	Phase 1

Detailed Description

ORIC-114 is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor of EGFR and HER2 alterations, including exon 20 insertion mutations.

This is a first-in-human, open-label, single arm, multicenter, dose escalation followed by dose expansion study to establish the recommended phase 2 dose (RP2D) and preliminary antitumor activity of ORIC-114 in patients with advanced solid tumors harboring an EGFR or HER2 alteration who have exhausted available treatment options

The study will begin with dose finding in patients with various solid tumors (Dose Escalation); additional dose expansion cohorts in specific tumor types (Dose Expansion), treatment history, and/or expression of a specific biomarker may be initiated via protocol amendment.

The study will evaluate escalating dose levels of ORIC-114 administered orally, once daily in 28-day cycles following an accelerated titration design used for Dose Level 1, after which, escalating doses of ORIC-114 will be administered following an interval 3+3 design.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Interval 3+3 dose escalation designInterval 3+3 dose escalation design
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Phase 1/1b, Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
• Actual Study Start Date: Mar 10, 2022
• Anticipated Primary Completion Date: Sep 1, 2023
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation ORIC-114 dosed orally on a continuous daily dosing regimen in 28-day cycles.	Drug: ORIC-114; ORIC-114 oral once daily for 28 days

Outcome Measures

Primary Outcome Measures

1. Recommended Phase 2 Dose (RP2D) [12 months]

   RP2D as determined by interval 3+3 dose escalation design

2. Maximum plasma concentration (Cmax) [28 Days]

   PK of ORIC-114

3. Time of maximum observed concentration (Tmax) [28 Days]

   PK of ORIC-114

4. Area under the curve (AUC) [28 Days]

   PK of ORIC-114

5. Apparent plasma terminal elimination half-life (t1/2) [28 Days]

   PK of ORIC-114

Secondary Outcome Measures

1. Objective response rate (ORR) [36 months]

   Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

2. Duration of response (DOR) [36 months]

   Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

3. Clinical benefit rate (CBR) [36 months]

   Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

4. Progression-free survival (PFS) [36 months]

   Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

5. Intracranial response rate (CR and/or PR) [36 months]

   Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

6. Intracranial progression-free survival (PFS) [36 months]

   Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Advanced or metastatic solid tumor with one of the following documented EGFR or HER2 insertions or mutations, including EGFR exon 20 insertion mutations, HER2 amplification or overexpression, and HER2 exon 20 insertion mutations, as determined by any local nucleic acid-based diagnostic testing method, or HER2 amplification/overexpression as determined by an immunohistochemistry (IHC) or an in situ hybridization (ISH) test

• Previously received available standard therapies and for whom additional standard therapy is considered unsuitable or intolerable

• Agreement and ability to undergo pretreatment biopsy

• Measurable disease according to RECIST 1.1

• CNS involvement which is either previously treated and controlled, or asymptomatic

• ECOG performance status of 0 or 1

• Adequate organ function

Exclusion Criteria:

• Known EGFR T790M mutation

• Leptomeningeal disease and spinal cord compression

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chungbuk University Hospital	Cheongju-si		Korea, Republic of
2	National Cancer Center	Goyang-si		Korea, Republic of
3	Catholic University of Korea, St, Vincent Hospital	Gyeonggi-do		Korea, Republic of
4	Gachon University Hospital	Incheon		Korea, Republic of
5	Seoul National Bundang Hospital	Seongnam-si		Korea, Republic of
6	Asan Medical Center	Seoul		Korea, Republic of
7	Samsung Medical Center	Seoul		Korea, Republic of
8	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of

Sponsors and Collaborators

• ORIC Pharmaceuticals

Investigators

• Study Director: Pratik S. Multani, MD, MS, ORIC Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ORIC Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05315700
• Other Study ID Numbers: ORIC-114-01
• First Posted: Apr 7, 2022
• Last Update Posted: Apr 19, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by ORIC Pharmaceuticals: EGFR alteration; HER2 alteration; exon 20 insertion mutation
• Additional relevant MeSH terms: Neoplasms

Study Results

No Results Posted as of Apr 19, 2022