Combining ORIC-114 with Amivantamab for NSCLC with EGFR Exon 20 Insertion Mutations

Phase 1b Study of ORIC-114 in Combination With Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC

Phase 1 Interventional ORIC Pharmaceuticals · NCT06816992

This study is testing a new combination of two drugs, ORIC-114 and amivantamab, to see if they can help people with advanced lung cancer that has a specific genetic mutation.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment76 (estimated)
Ages18 Years and up
SexAll
SponsorORIC Pharmaceuticals Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, radiation, amivantamab
Locations4 sites (New York, New York and 3 other locations)
Trial IDNCT06816992 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine the recommended phase 2 dose, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ORIC-114 when used in combination with subcutaneous amivantamab in patients with advanced or metastatic non-small cell lung cancer (NSCLC) that has an EGFR exon 20 insertion mutation. The study is open-label and single-arm, involving a dose escalation followed by dose expansion to assess the effectiveness of this combination therapy. ORIC-114 is a selective small molecule inhibitor designed to target specific mutations, while amivantamab is an antibody that targets EGFR and MET receptors, providing a dual approach to treatment.

Who should consider this trial

Good fit: Ideal candidates for this study are patients with histologically or cytologically confirmed metastatic NSCLC harboring an EGFR exon 20 insertion mutation.

Not a fit: Patients who have received prior therapies for their NSCLC or those with other types of EGFR mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could offer a new treatment option for patients with a specific type of NSCLC that is currently difficult to treat.

How similar studies have performed: Other studies have shown promise in targeting EGFR mutations in NSCLC, but the specific combination of ORIC-114 and amivantamab is a novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria
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:

* 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

Where this trial is running

New York, New York and 3 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Solid TumorsEGFR Exon 20 Insertion MutationsNSCLCEGFR-mutated NSCLCEGFR mutationsEGFR exon20EGFR exon 20 insertion mutationsORIC-114
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.