Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05315700




Registration number
NCT05315700
Ethics application status
Date submitted
24/03/2022
Date registered
7/04/2022
Date last updated
18/10/2024

Titles & IDs
Public title
Study of ORIC-114 in Patients with Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Scientific 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
Secondary ID [1] 0 0
ORIC-114-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ORIC-114
Treatment: Drugs - Chemotherapy drug

Experimental: Dose Escalation and Dose Optimization - ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles.

Experimental: Combination Dose Escalation - ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles.


Treatment: Drugs: ORIC-114
ORIC-114 oral daily

Treatment: Drugs: Chemotherapy drug
21 days for up to 4 cycles
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
Maximum plasma concentration (Cmax)
Timepoint [2] 0 0
28 Days
Primary outcome [3] 0 0
Time of maximum observed concentration (Tmax)
Timepoint [3] 0 0
28 Days
Primary outcome [4] 0 0
Area under the curve (AUC)
Timepoint [4] 0 0
28 Days
Primary outcome [5] 0 0
Apparent plasma terminal elimination half-life (t1/2)
Timepoint [5] 0 0
28 Days
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Duration of response (DOR)
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Clinical benefit rate (CBR)
Timepoint [3] 0 0
36 months
Secondary outcome [4] 0 0
Progression-free survival (PFS)
Timepoint [4] 0 0
36 months
Secondary outcome [5] 0 0
Intracranial response rate (CR and/or PR)
Timepoint [5] 0 0
36 months
Secondary outcome [6] 0 0
Intracranial progression-free survival (PFS)
Timepoint [6] 0 0
36 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2026
Actual
Sample size
Target
350
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 0 0
One Clinical Research, Hollywood Medical Centre - Nedlands
Recruitment hospital [4] 0 0
Sydney Adventist Health - Sydney
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Nedlands
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Hong Kong
State/province [14] 0 0
Shatin
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Cheongju-si
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Goyang-si
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Gyeonggi-do
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Incheon
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seongnam-si
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Poland
State/province [21] 0 0
Gdansk
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taipei
Country [23] 0 0
United Kingdom
State/province [23] 0 0
England

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ORIC Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05315700
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pratik S. Multani, MD, MS
Address 0 0
ORIC Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
ORIC Clinical
Address 0 0
Country 0 0
Phone 0 0
650-388-5600
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05315700