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

PHASE1PHASE2RECRUITING

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.

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Study details:

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).

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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

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

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-03-10

Primary completion: 2025-03-01

Study completion finish: 2026-03-01

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT05315700

Intervention or treatment

DRUG: ORIC-114

DRUG: Chemotherapy drug

Conditions

• Solid Tumors

Condition: Solid Tumors
DRUG: ORIC-114 and other drugs
Melbourne, Not Specified, Australia and more
Sponsor: ORIC Pharmaceuticals

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

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Find a site

Closest Location:

Peter MacCallum Cancer Centre

Research sites nearby

Select from list below to view details:

Peter MacCallum Cancer Centre
Melbourne, Not Specified, Australia
Chris O'Brien Lifehouse
Camperdown, Not Specified, Australia
One Clinical Research, Hollywood Medical Centre
Nedlands, Not Specified, Australia
Sydney Adventist Health
Sydney, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Dose Escalation and Dose Optimization ORIC-114 dosed orally on a continuous once daily dosing regimen in 28-day cycles.	DRUG: ORIC-114 ORIC-114 oral daily
EXPERIMENTAL: Combination Dose Escalation ORIC-114 dosed orally on a continuous once daily dosing regimen in 21-day cycles.	DRUG: ORIC-114 ORIC-114 oral daily

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Recommended Phase 2 Dose (RP2D)	RP2D as determined by interval 3+3 dose escalation design	12 months
Maximum plasma concentration (Cmax)	PK of ORIC-114	28 Days
Time of maximum observed concentration (Tmax)	PK of ORIC-114	28 Days
Area under the curve (AUC)	PK of ORIC-114	28 Days
Apparent plasma terminal elimination half-life (t1/2)	PK of ORIC-114	28 Days

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Objective response rate (ORR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Duration of response (DOR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Clinical benefit rate (CBR)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Progression-free survival (PFS)	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Intracranial response rate (CR and/or PR)	Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months
Intracranial progression-free survival (PFS)	Modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	36 months

Frequently Asked Questions

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You may be eligible to participate in this trial based on your search.Apply for study

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References

Clinical Trials Gov: Study of ORIC-114 in Patients with Advanced Solid Tumors Harboring an EGFR or HER2 Alteration