76 Participants Needed

ORIC-114 + Amivantamab for Non-Small Cell Lung Cancer

Recruiting at 4 trial locations
OC
Overseen ByORIC Clinical
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: ORIC Pharmaceuticals
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination ORIC-114 and Amivantamab for treating non-small cell lung cancer?

Amivantamab has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific genetic mutations, particularly when combined with other drugs like lazertinib or chemotherapy. It has been approved for use in patients with certain mutations who have not responded to previous treatments, demonstrating significant response rates and progression-free survival in clinical trials.12345

How does the drug ORIC-114 + Amivantamab differ from other treatments for non-small cell lung cancer?

The combination of ORIC-114 and Amivantamab is unique because Amivantamab is a bispecific antibody that targets both EGFR and MET, specifically designed for non-small cell lung cancer with EGFR exon 20 insertion mutations, which are typically resistant to other treatments. This combination aims to provide a new option for patients who have progressed after standard chemotherapy.23467

Research Team

PS

Pratik S. Multani, MD, MS

Principal Investigator

ORIC Pharmaceuticals

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific mutation called EGFR exon 20 insertion. Participants should have this type of lung cancer and be in good enough health to receive the treatments.

Inclusion Criteria

I have brain metastases but no symptoms.
I am fully active or restricted in physically strenuous activity but can do light work.
Measurable disease according to RECIST 1.1
See 5 more

Exclusion Criteria

My lung cancer has changed into small cell type.
I have received immunotherapy before.
I have had lung conditions that needed steroid treatment.
See 3 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ORIC-114 in combination with amivantamab to determine the recommended phase 2 dose (RP2D) through a 3+3 dose escalation design

12 months

Dose Expansion

Participants receive two potential ORIC-114 dose levels in combination with amivantamab to further assess safety and preliminary antitumor activity

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Amivantamab
  • ORIC-114
Trial OverviewThe study is testing different doses of a drug named ORIC-114 combined with another medication given as a shot under the skin, amivantamab. The goal is to find out the safest dose that works best (RP2D), how the body processes these drugs, their effects on tumors, and any potential benefits.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Part 2 Dose ExpansionExperimental Treatment2 Interventions
Two potential ORIC-114 dose levels + amivantamab
Group II: Part 1 Dose Escalation level 3Experimental Treatment1 Intervention
ORIC-114 + amivantamab
Group III: Part 1 Dose Escalation level 2Experimental Treatment1 Intervention
ORIC-114 + amivantamab
Group IV: Part 1 Dose Escalation level 1Experimental Treatment1 Intervention
ORIC-114 + amivantamab

Find a Clinic Near You

Who Is Running the Clinical Trial?

ORIC Pharmaceuticals

Lead Sponsor

Trials
9
Recruited
970+

Janssen Research and Development LLC

Collaborator

Trials
1
Recruited
80+

Findings from Research

In a phase 3 trial involving 308 patients with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions, the combination of amivantamab and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 11.4 months versus 6.7 months.
The combination therapy also showed a higher response rate, with 73% of patients achieving a complete or partial response compared to 47% in the chemotherapy-only group, indicating that amivantamab enhances the effectiveness of standard chemotherapy in this patient population.
Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions.Zhou, C., Tang, KJ., Cho, BC., et al.[2023]
Amivantamab, an EGFR-MET bispecific antibody, shows promise as a standard treatment for EGFR-mutant non-small cell lung cancer, particularly when combined with chemotherapy for patients with exon 20 mutations.
In comparison to the standard treatment osimertinib, amivantamab combined with lazertinib improved progression-free survival, although this benefit came with increased toxicity.
EGFR-Mutant NSCLC: Spotlight on Amivantamab.[2023]
Amivantamab is the first targeted therapy approved for non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations, showing promise for a group of mutations that typically have poor outcomes.
In the CHRYSALIS phase I trial, amivantamab demonstrated efficacy through its unique mechanism as a bispecific antibody targeting both EGFR and MET, although its large size may limit effectiveness against brain metastases.
Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer.Vyse, S., Huang, PH.[2022]

References

Amivantamab plus Lazertinib Is Efficacious in Non-Small Cell Lung Cancer. [2023]
Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023]
EGFR-Mutant NSCLC: Spotlight on Amivantamab. [2023]
Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer. [2022]
Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. [2022]
Amivantamab: First Approval. [2021]
Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. [2021]