PALOMA-2: A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the anti-tumor activity of amivantamab subcutaneous administered as a Co-Formulation (SC-CF) with recombinant human hyaluronidase PH20 (rHuPH20) (Cohorts 1, 2, and 3) in combination treatment and to characterize the safety of amivantamab SC-CF (Cohort 4).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Lung cancer is one of the most common types of cancer and is the most common cause of death from cancer. NSCLC accounts for 80 percent (%) to 85% of lung cancers with epidermal growth factor receptor (EGFR) mutations, the Exon 19 deletion (Exon19del) and Exon 21 leucine 858 to arginine substitution (Exon 21 L858R) point mutations. Amivantamab is a low-fucose, fully human immunoglobulin (IgG)1-based bispecific antibody directed against EGFR and mesenchymal-epithelial transition (MET) tyrosine kinase receptors. The rationale for this study is to collect efficacy, safety, and PK data to support the use of amivantamab SC-CF in regimens and populations currently under study and approved with the IV formulation of amivantamab. The study will include a screening phase (28 days), a treatment phase (21 days [Cohorts 2 and 3] or 28 days [Cohort 1 and 4]), and a follow up phase (after last study treatment until disease progression or death, whichever comes first). Safety assessments will include physical examinations, vital signs, electrocardiograms (ECGs), echocardiograms, ophthalmologic assessments (Cohorts 1 and 3 and in Cohort 4 [where applicable]), laboratory tests, adverse event (AE) frequency and severity (by Common Terminology Criteria for Adverse Events [CTCAE] v5.0) monitoring, and concomitant medication use (all cohorts). The total duration of the study is up to 1 year 6 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 (Exon19/L858R NSCLC First Line [1L] Previously Untreated): Amivantamab + Lazertinib Participants with treatment-naive locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) exon 19 deletion (exon19del) or exon 21 leucine 858 to arginine substitution (exon 21 L858R) mutation, will receive amivantamab SC-CF injection, 1600 milligrams (mg) and 2240 mg if body weight is greater than or equal to (>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily. |
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
Drug: Lazertinib
Lazertinib will be administered as an oral tablet.
Other Names:
|
| Experimental: Cohort 2 (Exon20 NSCLC, 1L Previously Untreated): Amivantamab + Pemetrexed + Carboplatin Participants with treatment-naive locally advanced or metastatic NSCLC harboring an EGFR exon20ins mutation will receive Amivantamab SC-CF injection 2560 mg and 3360 mg if body weight is >=80 kg on Cycle 1 Days 1, 8, and 15 and on Day 1 of each subsequent 21-day cycle, starting with Cycle 2 along with pemetrexed 500 milligrams per meter square (mg/m^2) as intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and IV infusion carboplatin area under the concentration-time curve 5 milligrams per milliliters (mg/mL) per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles. |
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
Drug: Carboplatin
Carboplatin will be administrated by IV infusion.
Drug: Pemetrexed
Pemetrexed will be administered by IV infusion.
|
| Experimental: Cohort 3 (Exon19/L858R NSCLC 2L Post Osimertinib):Amivantamab + Lazertinib+ Pemetrexed + Carboplatin Participants with locally advanced or metastatic NSCLC harboring an EGFR exon19del or exon 21 L858R mutation who have experienced disease progression on or after treatment with a third-generation EGFR tyrosine kinase inhibitor (TKI) (osimertinib), will receive amivantamab SC-CF injection 2560 mg and 3360 mg if body weight is >=80 kg on Cycle 1 Days 1, 8, and 15 and on Cycle 1 Days 1, 8, and 15 and on Day 1 of each subsequent 21-day cycle, starting with Cycle 2 along with lazertinib 240 mg orally once daily, pemetrexed 500 mg/m^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle up to 4 cycles, in combination with carboplatin for up to 4 cycles, then as maintenance until disease progression and IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles. |
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
Drug: Lazertinib
Lazertinib will be administered as an oral tablet.
Other Names:
Drug: Carboplatin
Carboplatin will be administrated by IV infusion.
Drug: Pemetrexed
Pemetrexed will be administered by IV infusion.
|
| Experimental: Cohort 4 (Previously Treated with Amivantamab IV): Switch from Amivantamab IV to SC-CF Participants who were previously on amivantamab IV once every 2 weeks (Q2W) regimen as part of standard of care, for at least 3 months, either as monotherapy or combination with lazertinib, will receive amivantamab SC-CF injection 1600 mg and 2240 mg if body weight is greater than or equal to 80 kg. |
Drug: Amivantamab
Amivantamab will be administered subcutaneously by manual injection.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Cohorts 1, 2, and 3: Objective Response Rate (ORR) Based on Investigator Assessment (INV) [Up to 1 year 6 months]
ORR based on INV will be reported. ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator.
- Cohort 4: Number of Participants with Adverse Events (AEs) [Up to 1 year 6 months]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
- Cohort 4: Number of Participants with AEs by Severity [Up to 1 year 6 months]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
- Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values [Up to 1 year 6 months]
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
- Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity [Up to 1 year 6 months]
Number of participants with laboratory values abnormalities which includes serum chemistry, hematology, coagulation, urinalysis, and serology) by severity will be reported. Severity of laboratory values abnormalities will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Secondary Outcome Measures
- Cohorts 1, 2, and 3: Number of Participants with AEs [Up to 1 year 6 months]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study.
- Cohorts 1, 2, and 3: Number of Participants with AEs by Severity [Up to 1 year 6 months]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
- Cohorts 1, 2, and 3: Number of Participants with Abnormalities in Clinical Laboratory Values [Up to 1 year 6 months]
Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported.
- Cohorts 1, 2, and 3: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity [Up to 1 year 6 months]
Number of participants with abnormalities in clinical laboratory values which includes serum chemistry, hematology, coagulation, urinalysis, and serology) by severity will be reported. Severity of laboratory values abnormalities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
- Cohorts 1, 2, and 3: ORR Based on Independent Central Review (ICR) [Up to 1 year 6 months]
ORR based on ICR will be reported. The ORR is defined as the percentage of participants who achieve a CR or PR, based on RECIST version 1.1, as confirmed by ICR.
- Cohorts 1, 2, and 3: Duration of Response (DoR) [Up to 1 year 6 months]
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR.
- Cohorts 1, 2, and 3: Time to Response (TTR) [Up to 1 year 6 months]
TTR (that is, time to first response) is defined as the time from the first dose of study treatment to the date of first documentation of a response (PR or CR) prior to any disease progression and subsequent anticancer therapy, based on RECIST version 1.1., for participants who have PR or CR as their best response.
- Cohorts 1, 2, and 3: Clinical Benefit Rate (CBR) [Up to 1 year 6 months]
CBR is defined as the percentage of participants achieving CR or PR, or durable standard deviation (SD) of a duration of at least 11 weeks as defined by RECIST version 1.1.
- Cohorts 1, 2, and 3: Progression-free Survival (PFS) [Up to 1 year 6 months]
The PFS is defined as the time from the first dose of study treatment until the date of objective disease progression or death, whichever comes first, based on RECIST version 1.1.
- Overall Survival (OS) [Up to 1 year 6 months]
The OS is defined as the time from the first dose of study treatment until the date of death due to any cause.
- Cohorts 1, 2, and 3: Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) of Amivantamab [Cycle 2 Day 1 of 28-day cycle]
Ctrough is defined as the serum concentration of amivantamab immediately prior to the next drug administration.
- Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Intravenous (TASQ-IV) [Up to 1 year 6 months]
Cancer therapy satisfaction will be assessed using the modified TASQ-IV. The modified TASQ is a 12-item questionnaire measuring the impact of each mode of treatment administration on five domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each of the domain/scale scores is scored on a 1-100 scale, where 0 is worst and 100 is best.
- Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC) [Up to 1 year 6 months]
Cancer therapy satisfaction will be assessed using the modified TASQ-SC. The modified TASQ is a 12-item questionnaire measuring the impact of each mode of treatment administration on five domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each of the domain/scale scores is scored on a 1-100 scale, where 0 is worst and 100 is best.
- Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Change (PGIC) Scale Score [Up to 1 year 6 months]
Patient-reported status as assessed by PGIC scale score will be reported. The PGIC is an assessment of the participant's overall sense of whether there has been a change since starting treatment. The PGIC is a 7-point response scale. Participants will be asked to rate their current fatigue as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse.
- Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score [Up to 1 year 6 months]
Patient-reported status as assessed by PGIS scale score will be reported. The PGIS is an assessment of lung cancer severity at a given point in time. The PGIS is a 5-point response scale. Participants will be asked to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-small cell lung cancer (NSCLC), characterized at the time of locally advanced or metastatic disease diagnosis. Additional Cohort specific disease requirements include: Cohorts 1 and 3: epidermal growth factor receptor (EGFR) exon 19 deletion (Exon19del) or L858R mutation; Cohort 2: EGFR Exon 20ins mutation EGFR Exon19del or Exon 21 L858R mutation (Cohort 1 and 3) or EGFR Exon 20 insertion mutation (Cohort 2) must have been identified as determined by Food and Drug Administration (FDA) approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United states [US]) or an accredited local laboratory (sites outside of the US). A copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor
-
Have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed
-
May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
-
Have adequate organ (renal, hepatic, hematological, coagulation and cardiac) functions
-
Participant must have eastern cooperative oncology group (ECOG) status of 0 or 1
-
A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility
Exclusion Criteria:
-
Participant has a medical history of interstitial lung disease (ILD), including drug induced ILD or radiation pneumonitis
-
Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort
-
Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against Coronavirus disease 19 (COVID-19) are not exclusionary
-
Cohorts 1, 3, and 4 (regimens potentially including lazertinib): Participant is currently receiving medications or herbal supplements known to be potent Cytochrome (CYP3A4/5) inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1
-
Other clinically active liver disease of infectious origin
-
Participant has a history of clinically significant cardiovascular disease including, but not limited to: a. diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following within 6 months prior to the first dose of study treatment(s): myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary. b. prolonged corrected QT interval by Fridericia (QTcF) interval greater than (>) 480 milliseconds (msec) or clinically significant cardiac arrhythmia or electrophysiologic disease (example, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate).c. uncontrolled (persistent) hypertension: systolic blood pressure >160 millimetre(s) of mercury (mmHg); diastolic blood pressure >100 mmHg. d. Congestive heart failure defined as NYHA class III-IV or hospitalization for congestive heart failure (CHF) (any New York Heart Association [NYHA] class) within 6 months of treatment initiation at Cycle 1/day 1 (C1D1). e. pericarditis/clinically significant pericardial effusion. f. myocarditis. g. baseline left ventricular ejection fraction (LVEF) below the institution's lower limit of normal at screening, as assessed by echocardiogram or multigated acquisition (MUGA) scan
-
Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (less than or equal to [<=] 10 milligrams per day [mg/day] prednisone or equivalent) for at least 2 weeks prior to treatment allocation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Kansas Cancer Center | Westwood | Kansas | United States | 66205 |
| 2 | Hunter Holmes McGuire Veterans Affairs Medical Center | Richmond | Virginia | United States | 23249 |
| 3 | Beijing Cancer Hospital of Peking University | Beijing | China | 100142 | |
| 4 | Jilin cancer hospital | Changchun | China | 130000 | |
| 5 | West China Hospital, Sichuan University | Chengdu | China | 610047 | |
| 6 | The First Affiliated Hospital, Sun Yat-sen University | Guangzhou | China | 510060 | |
| 7 | Sir Run Run Shaw Hospital, Zhejiang University School of Medicine | Hangzhou | China | 310016 | |
| 8 | Harbin medical university cancer hospital | Harbin | China | 150081 | |
| 9 | Liuzhou people's Hospital | Liuzhou | China | 545006 | |
| 10 | The First Affiliated Hospital of Wenzhou Medical University | Wenzhou | China | 325000 | |
| 11 | Yantai Yuhuangding Hospital | Yantai | China | 264000 | |
| 12 | Centre Francois Baclesse | Caen Cedex 05 | France | 14076 | |
| 13 | Centre Georges-François Leclerc | Dijon | France | 21079 | |
| 14 | Centre Leon Bérard | Lyon Cedex 8 | France | 69373 | |
| 15 | Institut Curie | PARIS Cedex 5 | France | 75248 | |
| 16 | Gustave Roussy | Villejuif Cedex | France | 94800 | |
| 17 | Evangelische Lungenklinik Berlin | Berlin | Germany | 13125 | |
| 18 | Universitaetsklinikum Koeln | Koeln | Germany | 50937 | |
| 19 | Klinikum Würzburg Mitte gGmbH Standort Missioklinik | Wuerzburg | Germany | 97074 | |
| 20 | Rambam Medical Center Department of Pediatric Pulmonology Meyer Childern's Hospital | Haifa | Israel | 3109601 | |
| 21 | Shizuoka Cancer Center | Shizuoka | Japan | 411-8777 | |
| 22 | The Cancer Institute Hospital of JFCR | Tokyo | Japan | 135-8550 | |
| 23 | Wakayama Medical University Hospital | Wakayama | Japan | 641-8510 | |
| 24 | University Malaya Medical Centre | Kuala Lumpur | Malaysia | 59100 | |
| 25 | Hospital Tengku Ampuan Afzan | Kuantan | Malaysia | 25100 | |
| 26 | Hospital Umum Sarawak | Kuching | Malaysia | 93586 | |
| 27 | Beacon Hospital Sdn. Bhd. | Petaling Jaya | Malaysia | 46050 | |
| 28 | Hosp. Univ. A Coruña | A Coruña | Spain | 15006 | |
| 29 | General University Hospital of Alicantet | Alacant | Spain | 03010 | |
| 30 | Hosp. Univ. Vall D Hebron | Barcelona | Spain | 08035 | |
| 31 | Hosp. Del Mar | Barcelona | Spain | 8003 | |
| 32 | Hosp. de La Santa Creu I Sant Pau | Barcelona | Spain | 8025 | |
| 33 | Inst. Cat. Doncologia-H Duran I Reynals | Barcelona | Spain | 8908 | |
| 34 | Hosp. Gral. Univ. Gregorio Marañon | Madrid | Spain | 28007 | |
| 35 | Hosp. Univ. Ramon Y Cajal | Madrid | Spain | 28034 | |
| 36 | Hosp. Univ. La Paz | Madrid | Spain | 28046 | |
| 37 | Hosp. Univ. 12 de Octubre | Madrid | Spain | 28051 | |
| 38 | Hosp. Regional Univ. de Malaga | Malaga | Spain | 29010 | |
| 39 | Hosp. Virgen Macarena | Sevilla | Spain | 41009 | |
| 40 | Hosp. Clinico Univ. de Valencia | Valencia | Spain | 46010 | |
| 41 | Hosp. Gral. Univ. Valencia | Valencia | Spain | 46014 | |
| 42 | Bristol Haematology and Oncology Centre | Bristol | United Kingdom | BS2 8ED | |
| 43 | Torbay Hospital-Devon | Devon | United Kingdom | TQ2 7AA | |
| 44 | Edinburgh Cancer Centre Western General | Edinburgh | United Kingdom | EH4 2XU | |
| 45 | Leicester Royal Infirmary | Leicester | United Kingdom | LE1 5WW | |
| 46 | University College London Hospitals | London | United Kingdom | NW1 2PG | |
| 47 | Sarah Cannon Research Institute | London | United Kingdom | W1G 6AD | |
| 48 | Southampton University Hospital | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR109264
- 2022-000526-21
- 61186372NSC2002