EGFR Exon 20 Insertion Mutations, EGFR-mutated NSCLC, NSCLC, Solid Tumors
Conditions
Keywords
NSCLC, EGFR mutations, EGFR exon20, EGFR exon 20 insertion mutations, ORIC-114, Amivantamab
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.
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
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
Sponsors
ORIC Pharmaceuticals
Janssen Research and Development LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Interval 3+3 dose escalation design followed by dose expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) | 12 months | RP2D of ORIC-114 in combination with amivantamab by interval 3+3 dose escalation design |
| Objective response rate (ORR) | 12 months | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Duration of response (DOR) | 12 months | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Progression-free survival (PFS) | 12 months | Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK parameters | 28 Days | Peak Plasma Concentration (Cmax) |
| BICR-Objective response rate (ORR) | 12 months | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM |
| BICR-Duration of response (DOR) | 12 months | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM |
| BICR-Progression-free survival (PFS) | 12 months | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM |
| Intracranial Objective response rate (ORR) | 12 months | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM |
| Intracranial Progression-free survival (PFS) | 12 months | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM |
Countries
Australia, Canada, United States
Contacts
CONTACTORIC Clinical
STUDY_DIRECTORPratik S. Multani, MD, MS
ORIC Pharmaceuticals
Outcome results
None listed