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RecruitingNCT06816992Updated Apr 24, 2026

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

A Phase 1 interventional study of ORIC-114 Dose 1 + amivantamab and ORIC-114 Dose 2 + amivantamab in Solid Tumors, EGFR Exon 20 Insertion Mutations and NSCLC, sponsored by ORIC Pharmaceuticals. Recruiting at 4 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-24.

Sponsored by ORIC Pharmaceuticals · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
76
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

ORIC-114, is a brain penetrant, selective, orally bioavailable, irreversible small molecule inhibitor designed to target EGFR exon 20 insertion mutations, making it a promising therapeutic candidate for development in patients whose tumors harbor these alterations, including those with CNS metastases.

Amivantamab is a bispecific EGFR-directed and MET receptor-directed antibody indicated in combination with carboplatin and pemetrexed for the first line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations and also as a single agent in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

This is an open-label, single arm, multicenter, dose escalation followed by dose expansion study to assess the safety and preliminary antitumor activity of ORIC-114 in combination with SC amivantamab, in patients with locally advanced or metastatic NSCLC harboring an EGFR exon 20 insertion mutations.

02

Conditions studied

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

Keywords

  • NSCLC
  • EGFR mutations
  • EGFR exon20
  • EGFR exon 20 insertion mutations
  • ORIC-114
  • Amivantamab
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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:

    1. Dose Escalation: Patients may have previously received and progressed on or after platinum-based chemotherapy or may be treatment naïve
    2. 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

Exclusion criteria

Exclusion Criteria:

  • 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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
76 participants (estimated)

Study arms

  • Experimental
    Part 1 Dose Escalation level 1

    ORIC-114 + amivantamab

    Drug: ORIC-114 Dose 1 + amivantamab

  • Experimental
    Part 1 Dose Escalation level 2

    ORIC-114 + amivantamab

    Drug: ORIC-114 Dose 2 + amivantamab

  • Experimental
    Part 1 Dose Escalation level 3

    ORIC-114 + amivantamab

    Drug: ORIC-114 Dose 3 + amivantamab

  • Experimental
    Part 2 Dose Expansion

    Two potential ORIC-114 dose levels + amivantamab

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

Interventions

  • DrugORIC-114 Dose 1 + amivantamab

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

  • DrugORIC-114 Dose 2 + amivantamab

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

  • DrugORIC-114 Dose 3 + amivantamab

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

05

What researchers measure

Primary outcomes

  1. Recommended Phase 2 Dose (RP2D)

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

    Time frame: 12 months

  2. Objective response rate (ORR)

    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Time frame: 12 months

  3. Duration of response (DOR)

    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Time frame: 12 months

  4. Progression-free survival (PFS)

    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Time frame: 12 months

Secondary outcomes

  1. Plasma PK parameters

    Peak Plasma Concentration (Cmax)

    Time frame: 28 Days

  2. Plasma PK parameters

    Time of maximal plasma concentration (Tmax)

    Time frame: 28 Days

  3. Plasma PK parameters

    Area under the plasma concentration vs time curve (AUC)

    Time frame: 28 Days

  4. Plasma PK parameters

    Apparent plasma terminal elimination half-life (t1/2)

    Time frame: 28 Days

  5. BICR-Objective response rate (ORR)

    Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM

    Time frame: 12 months

  6. BICR-Duration of response (DOR)

    Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM

    Time frame: 12 months

  7. BICR-Progression-free survival (PFS)

    Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM

    Time frame: 12 months

  8. Intracranial Objective response rate (ORR)

    Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM

    Time frame: 12 months

  9. Intracranial Progression-free survival (PFS)

    Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM

    Time frame: 12 months

06

Study locations

2 of 4 sites recruiting
  • 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
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06816992
Lead sponsor
ORIC Pharmaceuticals
Collaborators
Janssen Research and Development LLC
Responsible party
Sponsor
First posted
Feb 10, 2025
Start date
Feb 27, 2025
Primary completion
Dec 2026 (estimated)
Completion
Dec 2027 (estimated)
Last update
Apr 24, 2026

Study contacts

ORIC Clinical
Contact
clinical@oricpharma.com
650-388-5600
Pratik S. Multani, MD, MS
study director · ORIC Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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