ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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
- Prior Therapies: 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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1
Study ID
NCT06816992
Intervention or treatment
DRUG: ORIC-114 Dose 1 + amivantamab
DRUG: ORIC-114 Dose 2 + amivantamab
DRUG: ORIC-114 Dose 3 + amivantamab
Conditions
- Solid Tumors
- EGFR Exon 20 Insertion Mutations
- NSCLC
- EGFR-mutated NSCLC
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Peter MacCallum Cancer Centre
Select from list below to view details:
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
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Who is running the clinical trial?
ORIC Pharmaceuticals
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Part 1 Dose Escalation level 1
| Drug: ORIC-114 Dose 1 + amivantamab |
EXPERIMENTAL: Part 1 Dose Escalation level 2
| Drug: ORIC-114 Dose 2 + amivantamab |
EXPERIMENTAL: Part 1 Dose Escalation level 3
| Drug: ORIC-114 Dose 3 + amivantamab |
EXPERIMENTAL: Part 2 Dose Expansion
| Drug: ORIC-114 Dose 2 + amivantamab, Drug: ORIC-114 Dose 3 + amivantamab |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Plasma PK parameters | Peak Plasma Concentration (Cmax) | 28 Days |
| Plasma PK parameters | Time of maximal plasma concentration (Tmax) | 28 Days |
| Plasma PK parameters | Area under the plasma concentration vs time curve (AUC) | 28 Days |
| Plasma PK parameters | Apparent plasma terminal elimination half-life (t1/2) | 28 Days |
| BICR-Objective response rate (ORR) | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM | 12 months |
| BICR-Duration of response (DOR) | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM | 12 months |
| BICR-Progression-free survival (PFS) | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM | 12 months |
| Intracranial Objective response rate (ORR) | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM | 12 months |
| Intracranial Progression-free survival (PFS) | Blinded independent central review (BICR) according to RECIST 1.1 and RANO-BM | 12 months |
References
Clinical Trials Gov: ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLCOther trials to consider
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