ORIC-114 in Combination With Subcutaneous Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC

NCT06816992 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ORIC-114-05
• Study Type: interventional
• Target: 76
• Locations: 3 countries
• Sites: 4

Brief Summary

The purpose of this study is to establish the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutation.

Conditions

NSCLC; EGFR-mutated NSCLC; Solid Tumors; EGFR Exon 20 Insertion Mutations

Keywords

NSCLC; EGFR mutations; EGFR exon20; EGFR exon 20 insertion mutations; ORIC-114; Amivantamab

Outcome Measures

Primary Outcomes (4)

• Recommended Phase 2 Dose (RP2D)

  RP2D of ORIC-114 in combination with amivantamab by interval 3+3 dose escalation design

  12 months

• Objective response rate (ORR)

  Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  12 months

• Duration of response (DOR)

  Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  12 months

• Progression-free survival (PFS)

  Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  12 months

Secondary Outcomes (9)

• Plasma PK parameters

  28 Days

• Plasma PK parameters

  28 Days

• Plasma PK parameters

  28 Days

• Plasma PK parameters

  28 Days

• BICR-Objective response rate (ORR)

  12 months

Study Arms (4)

Part 1 Dose Escalation level 1

EXPERIMENTAL

ORIC-114 + amivantamab

Drug: ORIC-114 Dose 1 + amivantamab

Part 1 Dose Escalation level 2

EXPERIMENTAL

ORIC-114 + amivantamab

Drug: ORIC-114 Dose 2 + amivantamab

Part 1 Dose Escalation level 3

EXPERIMENTAL

ORIC-114 + amivantamab

Drug: ORIC-114 Dose 3 + amivantamab

Part 2 Dose Expansion

EXPERIMENTAL

Two potential ORIC-114 dose levels + amivantamab

Drug: ORIC-114 Dose 2 + amivantamab; Drug: ORIC-114 Dose 3 + amivantamab

Interventions

ORIC-114 Dose 3 + amivantamab DRUG

ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection

Part 1 Dose Escalation level 3; Part 2 Dose Expansion

ORIC-114 Dose 1 + amivantamab DRUG

ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection

Part 1 Dose Escalation level 1

ORIC-114 Dose 2 + amivantamab DRUG

ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection

Part 1 Dose Escalation level 2; Part 2 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed metastatic NSCLC with a documented EGFR exon 20 insertion mutation as determined locally by any nucleic acid-based diagnostic testing method; all tests should be performed in a CLIA certified or equivalently accredited laboratory
• Prior Therapies:
• Dose Escalation: Patients may have previously received and progressed on or after platinum-based chemotherapy or may be treatment naïve
• Dose Expansion: Patients must not have received any prior therapy; at time of enrollment, patients must decline, or be ineligible for all available standard of care therapies with proven benefit
• Agreement and ability to undergo a pretreatment biopsy, provided the procedure is clinically feasible and not deemed unsafe by the investigator
• Measurable disease according to RECIST 1.1
• Patients with asymptomatic CNS metastases are eligible
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function

You may not qualify if:

• Known small cell lung cancer transformation
• Leptomeningeal disease
• Spinal cord compression not definitively treated with surgery or radiation
• Prior immunotherapy
• Past medical history of interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
• Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact absorption of ORIC-114

Sponsors & Collaborators

• ORIC Pharmaceuticals: lead
• Janssen Research and Development LLC: collaborator

Study Sites (4)

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 03000, Australia

NOT YET RECRUITING

The Princess Margaret Hospital

Toronto, Ontario, M5G 1Z5, Canada

NOT YET RECRUITING

MeSH Terms

Interventions

amivantamab

Study Officials

• Pratik S. Multani, MD, MS

  ORIC Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

ORIC Clinical

CONTACT

650-388-5600; clinical@oricpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interval 3+3 dose escalation design followed by dose expansion

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 10, 2025
• Study Start: February 27, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); CA (1); US (2)