ORIC-114 in Combination With Subcutaneous Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: ORIC-114 Dose 1 + amivantamab, ORIC-114 Dose 2 + amivantamab, ORIC-114 Dose 3 + amivantamab.
- Who it may be relevant to
- Registry conditions: Solid Tumors, EGFR Exon 20 Insertion Mutations, NSCLC, EGFR-mutated NSCLC. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia, Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Phase 1b Study of ORIC-114 in Combination With Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC
Overview
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.
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.
Interventions
- Drug ORIC-114 Dose 1 + amivantamab
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection - Drug ORIC-114 Dose 2 + amivantamab
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection - Drug ORIC-114 Dose 3 + amivantamab
ORIC-114 oral daily, amivantamab subcutaneous weekly for 4 weeks followed by every 4 week injection
Primary outcome measures
- Recommended Phase 2 Dose (RP2D) [Time frame: 12 months]
- Objective response rate (ORR) [Time frame: 12 months]
- Duration of response (DOR) [Time frame: 12 months]
- Progression-free survival (PFS) [Time frame: 12 months]
Secondary outcome measures (9)
- Plasma PK parameters [Time frame: 28 Days]
- Plasma PK parameters [Time frame: 28 Days]
- Plasma PK parameters [Time frame: 28 Days]
- Plasma PK parameters [Time frame: 28 Days]
- BICR-Objective response rate (ORR) [Time frame: 12 months]
- BICR-Duration of response (DOR) [Time frame: 12 months]
- BICR-Progression-free survival (PFS) [Time frame: 12 months]
- Intracranial Objective response rate (ORR) [Time frame: 12 months]
- Intracranial Progression-free survival (PFS) [Time frame: 12 months]
Eligibility 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:
- 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
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 2 centers
- NYU Langone Health — New York
- Virginia Cancer Specialists — Fairfax
Australia · 1 center
- Peter MacCallum Cancer Centre — Melbourne
Canada · 1 center
- The Princess Margaret Hospital — Toronto
Identifiers
NCT: NCT06816992 · ORIC-114-05