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

Recruiting at 4 trial locations

Overseen By ORIC Clinical

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ORIC Pharmaceuticals

Must not be taking: Immunotherapy

Disqualifiers: Small cell lung cancer, ILD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced or metastatic non-small cell lung cancer (NSCLC) who have an EGFR exon 20 insertion mutation. The combination includes Amivantamab and ORIC-114, an experimental treatment. Researchers aim to determine the best dose for future studies and assess the safety and effectiveness of this treatment. Eligible participants have this type of lung cancer and have either tried standard treatments without success or haven't received any prior treatment and cannot undergo standard therapies. Participants must agree to a biopsy (a small tissue sample) before starting the treatment. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amivantamab is already approved for use in some lung cancer patients, indicating it has been tested and is generally safe when used alone. For ORIC-114, less information is available, but early studies are examining its safety in combination with amivantamab.

This trial, in its early stages, aims to determine the right dose and identify any side effects when using the two drugs together. Early trials primarily focus on how well participants tolerate the treatment, with any side effects typically being mild. This phase is crucial for identifying safety concerns before progressing to larger studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ORIC-114 combined with amivantamab for non-small cell lung cancer because it targets cancer in a new way. Unlike traditional treatments like chemotherapy, which attack fast-growing cells in general, this combination specifically targets EGFR and exon 20 insertion mutations, which are common in this type of lung cancer. This precision targeting could mean fewer side effects and better outcomes for patients. Additionally, the use of ORIC-114 aims to overcome resistance that sometimes develops with other therapies, potentially offering new hope for those who have limited options.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that amivantamab effectively treats non-small cell lung cancer (NSCLC) with specific genetic changes known as EGFR exon 20 insertion mutations. Studies have found that 73% of patients respond positively to this treatment. In this trial, participants will receive a combination of ORIC-114 and amivantamab. ORIC-114 targets the same genetic changes and may enhance the effects when used with amivantamab. This combination aims to provide a stronger treatment by focusing on the cancer's unique genetic traits. While researchers continue to study ORIC-114, the success of amivantamab offers a hopeful starting point. ^{1 2 3 5 6}

Who Is on the Research Team?

Pratik S. Multani, MD, MS

Principal Investigator

ORIC Pharmaceuticals

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• ORIC-114

Trial Overview The 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.

How Is the Trial Designed?

Group I: Part 2 Dose Expansion Experimental Treatment 2 Interventions

Two potential ORIC-114 dose levels + amivantamab

Group II: Part 1 Dose Escalation level 3 Experimental Treatment 1 Intervention

ORIC-114 + amivantamab

Group III: Part 1 Dose Escalation level 2 Experimental Treatment 1 Intervention

ORIC-114 + amivantamab

Group IV: Part 1 Dose Escalation level 1 Experimental Treatment 1 Intervention

ORIC-114 + amivantamab

Who Is Running the Clinical Trial?

ORIC Pharmaceuticals

Lead Sponsor

Trials

9

Recruited

970+

Janssen Research and Development LLC

Collaborator

Trials

1

Recruited

80+

Published Research Related to This Trial

Amivantamab, a bispecific antibody targeting EGFR and MET, received accelerated FDA approval for treating non-small cell lung cancer (NSCLC) patients with specific EGFR mutations, showing a 40% objective response rate in a Phase I/IB trial with a median response duration of 11.1 months.

In patients with other EGFR mutations, amivantamab alone had a 19% response rate, while combining it with lazertinib improved the response to 36%, indicating potential benefits of combination therapy in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations. Petrini, I., Giaccone, G.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab for the treatment of EGFR exon 20 insertion mutant non-small cell lung cancer. Vyse, S., Huang, PH.[2022]

Amivantamab, a bispecific antibody targeting EGFR-MET, has shown promising antitumor activity against non-small cell lung cancer (NSCLC) driven by EGFR exon 20 insertion mutations, which are typically resistant to standard EGFR tyrosine kinase inhibitors.

In preclinical models, amivantamab demonstrated superior efficacy compared to other treatments like cetuximab and poziotinib, and it produced significant tumor responses in patients with Exon20ins, indicating its potential as a new targeted therapy for this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Yun, J., Lee, SH., Kim, SY., et al.[2021]

Amivantamab is a bispecific monoclonal antibody that targets both EGFR and MET, specifically developed for treating non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations.

It received its first approval in the USA on May 21, 2021, for adult patients with advanced NSCLC who have progressed after platinum-based chemotherapy, and is currently in preregistration in multiple countries including the EU and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. Syed, YY.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. Zhou, C., Tang, KJ., Cho, BC., et al.[2023]

Citations

1. oricpharma.com oricpharma.com/news/oric-pharmaceuticals-announces-clinical-supply-agreement-to-evaluate-oric-114-in-combination-with-amivantamab-for-the-first-line-treatment-of-nsclc-with-egfr-exon-20-insertion-mutations/

Phase 1b combination trial of ORIC-114 and ... ORIC expects to initiate the combination Phase 1b trial to evaluate the safety and tolerability of ORIC-114 in combination with SC amivantamab ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06816992

Study Details | NCT06816992 | ORIC-114 in Combination ... 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025002302

Review Current paradigm of EGFR ins20 in non-small cell ... These results, along with an objective response rate of 73% in the combination group, contributed to the FDA approval of the combination regimen ...

4. investors.oricpharma.com investors.oricpharma.com/node/10401/pdf

ORIC® Pharmaceuticals Announces Publication in Cancer ... EGFR mutations are common oncogenic drivers in non-small cell lung cancer (NSCLC), and approximately 50% of patients may develop brain.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9899956/

Advances in the management of non-small-cell lung cancer ... The approval of amivantamab and mobocertinib for patients who have progressed after chemotherapy represents an important step forward in the management of these ...

6. firstwordpharma.com firstwordpharma.com/story/5936109

ORIC® Pharmaceuticals Reports Fourth Quarter and Full ... Presented preclinical data demonstrating potential best-in-class properties, including potency and selectivity, of ORIC-114 to treat NSCLC ...