Study to Evaluate Efficacy and Safety of Firmonertinib Compared With Investigator's Choice of EGFR Inhibitor as First-Line Treatment in Participants Who Have Locally Advanced or Metastatic NSCLC With EGFR P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arrivent Biopharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Feb 2026 → ongoing

Decision date (initial)

2025-12-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Others, Efficacy

1. To assess the anti-tumor activity of firmonertinib compared with investigator’s choice of osimertinib or afatinib in participants with locally advanced or metastatic NSCLC with EGFR PACC mutations

Conditions and MedDRA coding

Advanced or Metastatic Non-Small-Cell Lung Cancer With Epidermal Growth Factor Receptor P-Loop and Alpha C-Helix Compressing (PACC) Uncommon Mutations

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003485-PIP01-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Histologically or cytologically documented, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
2. 2. Documented results of the presence of an Epidermal Growth Factor Receptor (EGFR) PACC mutation in tumor tissue or blood from local testing.
3. 3. No prior systemic anticancer therapy regimens received for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) including prior treatment with any Epidermal Growth Factor Receptor (EGFR)-targeting agents (e.g., previous (EGFR) TKIs, monoclonal antibodies, or bispecific antibodies).
4. 4. Patients who have received prior neo-adjuvant and/or adjuvant chemotherapy, immunotherapy, or chemo radiotherapy for non-metastatic disease must have experienced a treatment free interval of at least 12 months.
5. 5. Patients with asymptomatic CNS metastases are eligible

Exclusion criteria 5

1. 1. Have NSCLC with any of the following EGFR mutations: exon 19 deletion, L858R, or C797S
2. 2. Have had prior treatment with EGFR-targeted agents (eg, EGFR-TKIs, EGFR-targeted proteolysis-targeting chimeras [PROTACs], monoclonal antibodies, or bispecific antibodies)
3. 3. Have had prior treatment with any systemic anti-cancer therapy for locally advanced or metastatic NSCLC not amenable to curative surgery or radiation, including chemotherapy, biologic therapy, immunotherapy, or any investigational drug
4. 4. Have had previous interstitial lung disease (ILD), including drug-induced ILD, or active ILD/active radiation pneumonitis
5. 5. Have a mean resting corrected QT interval (QTc) > 470 ms, obtained from triplicate electrocardiograms (ECGs) with QT interval corrected by Fridericia’s method (QTcF)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Progression Free Survival (PFS) determined by blinded independent central review (BICR)
2. 2. Confirmed overall response rate (ORR) as determined by BICR

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arrivent Biopharma Inc.

Sponsor organisation

Arrivent Biopharma Inc.

Address

18 Campus Boulevard Suite 100

City

Newtown Square

Postcode

19073-3240

Country

United States

Scientific contact point

Organisation

Arrivent Biopharma Inc.

Contact name

Vanessa Esquibel

Public contact point

Organisation

Arrivent Biopharma Inc.

Contact name

Vanessa Esquibel

Third parties 7

Locations

4 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 64 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications