Amivantamab mono, Evidenzprofil_CHRYSALIS
Lungenkarzinom · Version 5.1
| 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 (NCT02609776) | |||||
| Short Name | Design | Population | Intervention | Comparator | Outcomes |
|---|---|---|---|---|---|
| CHRYSALIS CR108064, 61186372EDI1001, 2018-003908-38 |
Nonrandomized, Parallel Assignment, Phase 1 Open Label study | Pretreated with Stage 4 and ECOG 0-1 Non-Small-Cell Lung Cancer for 2nd Line, 3rd Line or >3rd Line treatment | 1. Part 1:Amivantamab Monotherapy+Combination Dose Escalations (N=77)1 2. Part 2:Amivantamab Monotherapy+Combination Dose Expansion (N=285)2 3. Part 2: *Safety Population* Amivantamab Monotherapy+Combination Dose Expansion+EGFR Exon20ins mutation (N=114)3 4. Part 2: *Efficacy Population* Amivantamab Monotherapy+Combination Dose Expansion+EGFR Exon20ins mutation (N=81)4 |
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| Levels of Evidence | |||||
| GRADE | ⊕⊖⊖⊖a,b,c | We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect. | |||
| 1: The first cohort of participants will receive intravenous (IV) infusions of Amivantamab 140 milligram (mg) as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level. Dose escalation will continue until maximum tolerated dose is reached or all planned doses are administered. Participants will receive IV infusion of Amivantamab once weekly during cycle 1 and once every 2 weeks during subsequent cycles (duration of each treatment cycle is 28 days). Participants will receive lazertinib and Amivantamab on Cycle 1 Day 1 (C1D1) prior to initiation of Amivantamab (C1D1) at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily thereafter, on 28-day Amivantamab treatment cycle. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with standard of care carboplatin and pemetrexed.; 2: Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. The purpose of dose expansion is to further evaluate safety, tolerability, pharmacokinetic, and to assess preliminary efficacy in monotherapy and combination therapy cohorts.; 3: Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. With EGFR Exon20ins mutation and previous platinum-based chemotherapy; 4: Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. With EGFR Exon20ins mutation and previous platinum-based chemotherapy with ≥3 disease assessments at clinical cutoff | |||||
| a: Open Label Study;b: Non-Randomized Study;c: Studydesign - Phase I | |||||
| Outcome | Part 2: *Safety Population* Amivantamab Monotherapy+Combination Dose Expansion+EGFR Exon20ins mutation N=114 |
GRADE | |
|---|---|---|---|
| Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer (Safety Population) Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. : Park, K 2021. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.. ; 39 (30); 3391-3402* | |||
| Dichotomous Outcomes | |||
| AE (Any) | N=114 | 113 (99.12%) | ⊕⊖⊖⊖ |
| AE (CTCAE ≥3) | N=114 | 40 (35.09%) | ⊕⊖⊖⊖ |
| AE-D (Any) | N=114 | 8 (7.02%) | ⊕⊖⊖⊖ |
| AE-Disc (Any) | N=114 | 11 (9.65%) | ⊕⊖⊖⊖ |
| SAE (Any) | N=114 | 34 (29.82%) | ⊕⊖⊖⊖ |
| Outcome | Part 2:Amivantamab Monotherapy+Combination Dose Expansion N=285 |
GRADE | |
| Amivantamab in Patients with Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy treated at the recommended phase II dose (RP2D): Park, K 2021. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.. ; 39 (30); 3391-3402** | |||
| Dichotomous Outcomes | |||
| AE (Any) | N=258 | 257 (99.61%) | ⊕⊖⊖⊖ |
| AE (CTCAE ≥3) | N=258 | 101 (39.15%) | ⊕⊖⊖⊖ |
| AE-D (Any) | N=258 | 13 (5.04%) | ⊕⊖⊖⊖ |
| AE-Disc (Any) | N=258 | 17 (6.59%) | ⊕⊖⊖⊖ |
| SAE (Any) | N=258 | 79 (30.62%) | ⊕⊖⊖⊖ |
| Outcome | Part 2: *Efficacy Population* Amivantamab Monotherapy+Combination Dose Expansion+EGFR Exon20ins mutation N=81 |
GRADE | |
| Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer (Efficacy Population) Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.: Park, K 2021. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.. ; 39 (30); 3391-3402*** | |||
| Dichotomous Outcomes | |||
| OS - Time To Event | N=81 | 22.8 [14.6; ] | ⊕⊖⊖⊖ |
| PFS - Time To Event | N=81 | 8.3 [6.5; 10.9] | ⊕⊖⊖⊖a |
| DOR - Time To Event | N=81 | 11.1 [6.9; ] | ⊕⊖⊖⊖ |
| ORR - TuDD | N=81 | 40 (49.38%) | ⊕⊖⊖⊖ |
| Age | |||
| <65 | N=48 | 21 (43.75%) | |
| ≥65 | N=33 | 11 (33.3333%) | |
| Baseline ECOG PS | |||
| ≥1 | N=55 | 18 (32.7273%) | |
| 0 | N=26 | 14 (53.8462%) | |
| History of brain metastases | |||
| No | N=63 | 25 (39.6825%) | |
| Yes | N=18 | 7 (38.8889%) | |
| History of smoking | |||
| No | N=43 | 19 (44.186%) | |
| Yes | N=38 | 13 (34.2105%) | |
| Previous EGFR TKI | |||
| No | N=61 | 22 (36.0656%) | |
| Yes | N=20 | 10 (50%) | |
| Previous immunotherapy | |||
| No | N=44 | 15 (34.0909%) | |
| Yes | N=37 | 17 (45.9459%) | |
| Previous lines of therapy | |||
| ≥3 | N=26 | 15 (57.6923%) | |
| 1 | N=31 | 10 (32.2581%) | |
| 2 | N=24 | 7 (29.1667%) | |
| Race | |||
| Asian | N=40 | 17 (42.5%) | |
| Non-Asian | N=32 | 14 (43.75%) | |
| Sex | |||
| Female | N=48 | 17 (35.4167%) | |
| Male | N=33 | 15 (45.4545%) | |
| *Database cutoff: 07.06.2020 **Database cutoff: 07.06.2020 ***Database cutoff: 07.10.2020 |
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| a: Missing individual analysis of combined endpoint componenets (progression) | |||
| AE: Adverse Events; AE-D: Adverse Events Leading to Death; AE-Disc: Adverse Events Leading to Treatment Discontinuation; Any: Any Grade; CTCAE ≥3: Common Terminology Criteria for Adverse Events, Grade ≥3; DOR: Duration Of Response; ORR: Objective Response Rate; OS: Overall Survival; PFS: Progression-Free Survival; SAE: Serious Adverse Events; TuDD: Time to Definitive Deterioration | |||