Clinical trial NCT06816992: ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC
Official title: Phase 1b Study of ORIC-114 in Combination with Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: 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
Lead sponsor: ORIC Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research and Development LLC
First posted: 2025-02-10
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Interval 3+3 dose escalation design followed by dose expansion
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: 12 months
measure: Objective response rate (ORR)
timeFrame: 12 months
measure: Duration of response (DOR)
timeFrame: 12 months
measure: Progression-free survival (PFS)
timeFrame: 12 months
Secondary outcomes:
measure: Plasma PK parameters
timeFrame: 28 Days
measure: Plasma PK parameters
timeFrame: 28 Days
measure: Plasma PK parameters
timeFrame: 28 Days
measure: Plasma PK parameters
timeFrame: 28 Days
measure: BICR-Objective response rate (ORR)
timeFrame: 12 months
measure: BICR-Duration of response (DOR)
timeFrame: 12 months
measure: BICR-Progression-free survival (PFS)
timeFrame: 12 months
measure: Intracranial Objective response rate (ORR)
timeFrame: 12 months
measure: Intracranial Progression-free survival (PFS)
timeFrame: 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Toronto
country: Canada
facility: The Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: ORIC Pharmaceuticals
name: Pratik S. Multani, MD, MS
role: STUDY_DIRECTOR
References: