SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02609776

Developed by Shray Alag, 2019.
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 this study is to evaluate the safety and pharmacokinetics, establish a recommended phase 2 dose (RP2D) regimens, and to assess the preliminary efficacy of JNJ-61186372 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

2 Interventions

Name: JNJ-61186372

Description: The first cohort of participants will receive intravenous infusions of JNJ-61186372 at a dose of 140 milligram (mg). Each subsequent cohort will receive intravenous infusions of JNJ-61186372 at an increased dose level. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered. Participants will receive intravenous infusion of JNJ-61186372 once weekly during cycle 1 and once every 2 weeks during subsequent cycles. The duration of each treatment cycle is 28 days.

Type: Drug

Part 1: Dose Escalation

Name: JNJ-61186372

Description: Participants will receive intravenous infusions of JNJ-61186372 at a recommended Phase 2 dose (RP2D) regimen. The duration of each treatment cycle is 28 days.

Type: Drug

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

Time: Screening up to follow-up (30 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: Percentage of Participants With Clinical Benefit

Time: Up to End of Treatment Follow Up Period (30 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: Overall Response Rate (ORR)

Time: Up to End of Treatment Follow Up Period (30 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: Duration of Response (DOR)

Time: Up to End of Treatment Follow Up Period (30 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)

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: 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 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 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 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

Participants must have either progressed after receiving prior therapy for metastatic disease, or be ineligible for, or have refused all other currently available therapeutic options - 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 and MET-1], as well as marketed tyrosine kinase inhibitor [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 ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1