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Report for Clinical Trial NCT02609776

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of JNJ-61186372 as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D)(monotherapy) and recommended Phase 2 combination dose (RP2CD) (combination therapy) in participants with advanced non-small cell lung cancer (NSCLC).

NCT02609776 Non-Small-Cell Lung Cancer
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

3 Interventions

Name: JNJ-61186372

Description: The first cohort of participants will receive IV infusions of JNJ-61186372 140 mg as monotherapy. Each subsequent cohort will receive IV infusions of JNJ-61186372 at increased dose level until maximum tolerated dose is reached or all planned doses are administered. Participants will receive lazertinib and JNJ-61186372 at predefined dose levels, based upon observed safety and protocol defined criteria. The duration of each treatment cycle is 28 days.

Type: Drug

Part 1:JNJ-61186372 Monotherapy+Combination Dose Escalations

Name: JNJ-61186372

Description: Participants will receive IV infusion of JNJ-61186372 as monotherapy at RP2D regimen or in combination lazertinib at RP2CD regimen as determined in Part 1.

Type: Drug

Part 2:JNJ-61186372 Monotherapy+Combination Dose Expansion

Name: Lazertinib

Description: Lazertinib will be administered in combination with JNJ-61186372 at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily on the 28-day JNJ-61186372 treatment cycle.

Type: Drug

Part 1:JNJ-61186372 Monotherapy+Combination Dose Escalations Part 2:JNJ-61186372 Monotherapy+Combination Dose Expansion


Primary Outcomes

Description: The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.

Measure: Part 1: Number of Participants With Dose Limiting Toxicity (DLT)

Time: Up to Day 28

Description: An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Measure: Part 2: Number of Participants With Adverse Events (AEs) and Serious AEs

Time: Screening up to follow-up (30 [+7] days after the last dose)

Description: Overall response rate (ORR) is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). CR: disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (< 10 mm short axis) and normalisation of tumour marker levels; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Measure: Part 2: Overall Response Rate (ORR)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: DOR will be calculated as time from initial response of CR (disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size ([<] 10 [mm] short axis) and normalisation of tumour marker levels) or PR (at least a 30 [%] decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits) to progressive disease (PD) or death due to underlying disease, whichever comes first, only for participants who achieve CR or PR.

Measure: Part 2: Duration of Response (DOR)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: Clinical benefit rate is defined as the percentage of participants achieving complete response (CR): disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (less than [<] 10 millimeter [mm] short axis) and normalisation of tumour marker levels or partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Measure: Part 2: Percentage of Participants With Clinical Benefit

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Secondary Outcomes

Description: The Cmax is the maximum observed serum concentration of JNJ-61186372.

Measure: Maximum Serum Concentration (Cmax) of JNJ-61186372

Time: Cycle 1 Day 1: predose through end of infusion (EOT) or Follow Up (approximately 16 months) (each cycle is of 28 days)

Description: The Tmax is defined as time to reach maximum observed serum concentration of JNJ-61186372.

Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The AUC(t1-t2) is the area under the serum JNJ-61186372 concentration-time curve from time t1 to t2.

Measure: Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

Measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: Cmax is the maximum observed serum concentration of lazertinib.

Measure: Maximum Serum Concentration (Cmax) of Lzertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: Tmax is defined as time to reach maximum observed serum concentration of lazertinib.

Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Lazertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of Lazertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.

Measure: Accumulation ratio (R) of JNJ-61186372

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: Serum levels of antibodies to JNJ-61186372 for evaluation of potential immunogenicity.

Measure: Number of Participants With Anti-Drug Antibodies (ADA)

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: PFS is defined as the time from first infusion of study drug to PD or death due to any cause.

Measure: Progression-Free Survival (PFS)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: TTF is defined as the time from the first infusion of the study drug to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond RECIST v1.1 defined disease progression.

Measure: Time to Treatment Failure (TTF)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: OS is defined as the time from first infusion of study drug to death due to any cause.

Measure: Overall Survival (OS)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 C797S

Cohort C: Participants with primary EGFR mutated disease, with a documented EGFR alteration (example, C797S) mediating resistance to previous treatment with a third generation EGFR TKI (for example, osimertinib), in participants with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (for example, poziotinib). --- C797S ---


2 L858R

In cases where participants refuse currently available therapeutic options, this must be documented in the study records - For Part 1 Combination Dose Escalation only: Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) be treatment naïve for metastatic disease, without access to third generation TKI in the front-line setting, or (b) have progressed after front-line treatment with first (erlotinib or gefitinib) or second generation (afatinib) TKI and are ineligible for Cohort MET-1, or (c) have been treated with a third generation TKI (eg, osimertinib) in either the front line or second-line setting, and are not eligible for enrollment in either Cohort C or MET-1 For Part 2 only: Participants must also have disease with a previously diagnosed activating epidermal growth factor receptor (EGFR) mutation (includes both inhibitor sensitive primary mutations such as Exon 19 deletion and L858R (Cohort C, E, and MET-1), as well as marketed TKI-resistant mutations such as Exon 20 insertion (Cohort C, D and MET-1) or activating cMet Exon 14 skipping mutation (Cohort MET-2). --- L858R ---

In cases where participants refuse currently available therapeutic options, this must be documented in the study records - For Part 1 Combination Dose Escalation only: Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation and (a) be treatment naïve for metastatic disease, without access to third generation TKI in the front-line setting, or (b) have progressed after front-line treatment with first (erlotinib or gefitinib) or second generation (afatinib) TKI and are ineligible for Cohort MET-1, or (c) have been treated with a third generation TKI (eg, osimertinib) in either the front line or second-line setting, and are not eligible for enrollment in either Cohort C or MET-1 For Part 2 only: Participants must also have disease with a previously diagnosed activating epidermal growth factor receptor (EGFR) mutation (includes both inhibitor sensitive primary mutations such as Exon 19 deletion and L858R (Cohort C, E, and MET-1), as well as marketed TKI-resistant mutations such as Exon 20 insertion (Cohort C, D and MET-1) or activating cMet Exon 14 skipping mutation (Cohort MET-2). --- L858R --- --- L858R ---

Cohort E (combination JNJ-61186372 and lazertinib): Participants must have been diagnosed with EGFR Exon 19del or L858R activating mutation, and have progressed after first or second-line treatment with a third generation TKI (eg, osimertinib) - Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria: - Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension, or diabetes, ongoing or active infection, (that is, has discontinued all antibiotics for at least one week prior to first dose of study drug), or psychiatric illness/social situation that would limit compliance with study requirements. --- L858R ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 61
REST GPC3 WT1 HPGD BRAF PIK3CA TP53 TRIM28 RB1 TRIP13 SLCO2A1 AKT1 CASP8 KRAS TSC1 POU6F2 EWSR1 PRKN LMNA NAB2 TERT TSC2 SLC22A18 BRCA2 PPP2R1B STAT6 STK11 MUC5B ERBB2 TSC2 MBTPS2 BAP1 TSC2 DICER1 PDGFRB PERP EGFR TSC1 DIS3L2 NOTCH3 KEAP1 DICER1 DICER1 WT1 TSC1 C11ORF95 IRF1 CYP2A6 WRN RELA WT1 PTEN SFTPC SFTPA2 ERCC6 TRPV3 TP53 H19 TRIM28 FASLG MAP3K8
Non-small cell lung carcinoma
Genes 3
TP53 TP53 BAP1