A Clinical Study of Amivantamab and Lazertinib in Combination with Platinum-Based Chemotherapy Compared with Platinum-Based Chemotherapy in Patients with EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Nov 2021 → ongoing

Decision date (initial)

2024-02-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-506518-33-00

EudraCT number

2021-001825-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Others, Safety, Pharmacokinetic, Pharmacodynamic

1. To assess the efficacy of lazertinib, amivantamab, carboplatin, and
pemetrexed ( LACP/ACP-L), compared with carboplatin and pemetrexed
(CP), in participants with locally advanced or metastatic epidermal
growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution
NSCLC.
2. To assess the efficacy of ACP, as compared with CP, in participants
with locally advanced or metastatic EGFR Exon 19del or Exon 21 L858R
substitution NSCLC.

Conditions and MedDRA coding

Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparecy. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1. At least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place).
2. 10. A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
3. 11. A participant must be either of the following: a. Not of childbearing potential; or b. Of childbearing potential and • practicing true abstinence during the entire period of the study, including up to 7 months after the last dose of study treatment is given; or • have a sole partner who is vasectomized; or • practicing at least 1 highly effective user independent method of contraception. Participant must agree to continue contraception throughout the study and through 6 months after the last dose of study treatment.
4. 12. A participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment.
5. 2. Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous NSCLC, characterized at or after the time of locally advanced metastatic disease diagnosis by either EGFR Exon 19del or Exon 21 L858R mutation, by an FDA-approved or other validated test of either ctDNA or tumor tissue in a CLIA certified laboratory (sites in the US) or an accredited local laboratory (sites outside of the US). A de-identified copy of the initial test report documenting the EGFR mutation must be included in the participant records and must be submitted to the sponsor during the Screening Phase. If provision of this report is not permitted by the site or local policies, then sponsor-approved equivalent documentation must be provided.
6. 3. Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first line treatment for locally advanced or metastatic disease or in the second line setting after prior treatment with first- or second-generation EGFR TKI as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 halflives) prior to randomization (ie, last dose no later than Day -8).
7. 4. Participant must have at least 1 measurable lesion, according to RECIST v1.1, that has not been previously irradiated. Measurable lesions should not have been biopsied during screening, but if only 1 nonirradiated measurable lesion exists, it may undergo the optional diagnostic biopsy and be acceptable as a target lesion, provided the baseline tumor assessment scans are performed at least 14 days after the biopsy.
8. 5. Participants with a history of brain metastases must have had all lesions treated as clinically indicated (ie, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization and the participant can be receiving no greater than 10 mg rednisone or equivalent daily for the treatment of intracranial disease.
9. 6. Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
10. 7. Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion, platelet transfusion, erythropoietin stimulating agents, or platelet-boosting treatments within 7 days prior to the date of the laboratory test: • Hemoglobin ≥10 g/dL • Absolute neutrophil count ≥1.5×10^9/L, without use of G-CSF within 10 days prior to the date of the test • Platelets ≥100×10^9/L • ALT and AST ≤3×upper limit of normal (ULN) • Total bilirubin ≤1.5×ULN if no liver metastasis, or ≤3×ULN in the presence of liver metastasis (participants with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits) • Creatinine clearance >50 mL/min as measured or calculated by Cockcroft-Gault formula
11. 8. Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade ≤2 peripheral neuropathy, or Grade ≤2 hypothyroidism stable on hormone replacement).
12. 9. Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
13. 13. A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. A participant who is sexually active with a participant of childbearing potential must agree to use a condom and the partner must also be practicing a highly effective method of contraception. A participant who is vasectomized must still use a condom for prevention of passage of exposure through ejaculation, but the participant’s partner is not required to use contraception.
14. 14. A participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 6 months after receiving the last dose of study treatment. Participants should be advised to consider preservation of sperm prior to treatment with pemetrexed or carboplatin, as these agents may impair fertility.
15. 15. Participant must be willing and able to adhere to the lifestyle restrictions specified in this protocol.

Exclusion criteria 12

1. 1. Participant has an uncontrolled illness, including but not limited to: • Uncontrolled diabetes • Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics at least 1 week prior to starting study treatment] or diagnosed or suspected viral infection), except as allowed by Exclusion Criterion 17 for HIV • Active bleeding diathesis • Impaired oxygenation requiring continuous oxygen supplementation • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of study treatment • Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements • Any ophthalmologic condition that is clinically unstable
2. 2. Participant received prior systemic anticancer therapy in the locally advanced or metastatic setting, or in the adjuvant setting, for the same nonsquamous NSCLC intended for treatment now, except as allowed by Inclusion Criterion 3.
3. 3. Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization.
4. 4. Participants with symptomatic or progressive brain metastases.
5. 5. Participant previously enrolled in the Sponsor's study 73841937NSC3003 (NCT04487080).
6. 6. Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation.
7. 7. Participant has known small cell transformation.
8. 8. Participant has uncontrolled tumor-related pain. Symptomatic lesions amenable to palliative radiotherapy (eg, bone metastases, or metastases causing nerve impingement) should be treated at least 14 days prior to randomization.
9. 9. Participant has a medical history of ILD, including drug induced ILD or radiation pneumonitis.
10. 10. Participant has a history of hypersensitivity to carboplatin or pemetrexed, or to any excipient of carboplatin, pemetrexed, amivantamab, or lazertinib.
11. 11. Participant has an active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. Exceptions include participants who have undergone curative therapy and have no evidence of disease recurrence since completion of that therapy, and those with local cancers that have been apparently cured such as: a. Non-muscle invasive bladder cancer (NMIBC) treated within the last 24 months that is considered completely cured. b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. c. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured. d. Localized prostate cancer (N0M0): • with a Gleason score of 6, treated within the last 24 months or untreated and under surveillance, • with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, • or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence. e. Breast cancer: • lobular carcinoma in situ or ductal carcinoma in situ that is considered completely cured, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence. f. Other malignancy that is considered cured with minimal risk of recurrence.
12. 12. Participant has any contraindication to treatment with pemetrexed or carboplatin or participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Progression-free survival (PFS) using RECIST v1.1 guidelines, as assessed by blinded independent central review (BICR).

Investigational products

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

Test 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 16

Locations

12 EU/EEA countries · 51 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 160 files

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

Application history

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