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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ORIC Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jan 2025 → ongoing

Decision date (initial)

2024-09-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ORIC Pharmaceuticals Inc.

External identifiers

EU CT number

2024-512264-66-00

ClinicalTrials.gov

NCT05315700

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Others, Therapy, Dose response, Efficacy

Part I: To assess the safety and tolerability of ORIC-114 as a single agent
Part II: To select the optimal ORIC-114 RP2D for Phase 2 expansion cohorts
Part III: To assess the safety and tolerability of ORIC-114 in combination with carboplatin-pemetrexed
Parts I, II, & III: To assess the pharmacokinetics (PK) of ORIC-114

Secondary objectives 4

1. Parts I & II: To evaluate the preliminary antitumor activity of ORIC-114 as a single agent
2. Part III: To evaluate the preliminary antitumor activity of ORIC-114 in combination with carboplatin-pemetrexed
3. Parts I & II: To determine the preliminary intracranial activity of ORIC-114 in patients presenting with brain lesions at baseline
4. Part III: To determine the preliminary intracranial activity of ORIC-114 in combination with carboplatin-pemetrexed in patients presenting with brain lesions at baseline

Conditions and MedDRA coding

Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Aged ≥18 years at the time of signing the informed consent
2. 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 described in the protocol.
3. Prior Therapies as described in the protocol.
4. Agreement and ability to undergo pretreatment biopsy, provided the procedure is clinically feasible and not deemed unsafe by the investigator
5. Measurable disease according to RECIST 1.1
6. Patients with CNS involvement, which is either previously treated and controlled or untreated and asymptomatic are eligible.
7. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study drug are eligible.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Adequate organ function as defined by the criteria included in the protocol.
10. Able to swallow oral medication without chewing or crushing.
11. Women of childbearing potential must have a negative serum pregnancy test within 72 hours before starting study treatment.
12. Women of childbearing potential and men who are not surgically sterile must agree to use highly effective medically accepted method of birth control during the study and for 90 days after end of treatment.
13. Willing and able to give informed consent and comply with protocol requirements for the duration of the study.

Exclusion criteria 12

1. Patients with known EGFR T790M mutation.
2. Current participation in another clinical study of an investigational agent, vaccine, or device; concomitant participation in observational studies is acceptable after sponsor approval.
3. Leptomeningeal disease (LMD) and spinal cord compression.
4. Treated with any other anticancer therapy or herbal (alternative) medicines within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug.
5. Radiotherapy within 2 weeks prior to first dose of study drug (palliative radiation or stereotactic radiosurgery within 7 days prior to first dose of study drug); patients must have recovered from all radiotherapy-related toxicities.
6. Major surgery within 21 days prior to first dose of study drug or incomplete recovery from adverse effects resulting from such procedure.
7. 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 of first dose of study.
8. Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
9. Known human immunodeficiency virus (HIV) infection, unless patient is healthy and has a low risk of AIDS-related outcomes.
10. 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. Testing is not required in the absence of history.
11. Active gastrointestinal disease (eg, Crohn’s disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption.
12. Any other concurrent serious uncontrolled medical, psychological, or addictive conditions that, in the opinion of the investigator, may interfere with protocol compliance or contraindicates participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Part I: Provisional RP2Ds and/or MTD of ORIC-114.
2. Part II: Optimal ORIC-114 RP2D.
3. Part III: RP2D and/or MTD of ORIC-114 in combination with carboplatin-pemetrexed
4. Incidence of adverse events, vital signs, evaluation of clinical laboratory results, 12-lead electrocardiogram (ECG), and other clinical assessments.
5. PK profile as measured by Tmax, Cmax, Clast, AUClast, AUCtau, AUCinf, Kel, t1/2, CL/F, Vz/F, Rac(Cmax), and Rac(AUC) as appropriate

Secondary endpoints 3

1. Assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 • Objective response rate (ORR) (complete response [CR] or partial response [PR]), measured as changes in target and non-target lesions relative to baseline every 8 weeks • Duration of response (DOR), defined as time of first response to first documentation of radiographic progression or death, whichever occurs first.
2. • Clinical benefit rate (CBR) (CR, PR, or stable disease [SD] ≥6 months) • Progression-free survival (PFS), defined as time from first dose of ORIC-114 to first documentation of radiographic progression or death, whichever occurs first
3. Intracranial response will be assessed according to modified RECIST 1.1 and/or RANO-BM • Intracranial response rate (CR or PR) measured as changes in target and non-target CNS lesions • Intracranial PFS, defined as time from first dose of ORIC-114 to first documentation of radiographic progression in the brain or death, whichever occurs first.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ORIC Pharmaceuticals Inc.

Sponsor organisation

ORIC Pharmaceuticals Inc.

Address

240 East Grand Avenue

City

South San Francisco

Postcode

94080-4811

Country

United States

Scientific contact point

Organisation

ORIC Pharmaceuticals Inc.

Contact name

Pratik Multani

Public contact point

Organisation

ORIC Pharmaceuticals Inc.

Contact name

ORIC Clinical

Third parties 7

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications