A Phase 2, Multicenter, Randomized, Open-Label Trial of GEN1046 as Monotherapy and in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer After Treatment With Standard of Care Therapy With an Immune Checkpoint Inhibitor

Phase 2

• Conditions: NSCLC; Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer; 10038667; 10029107

• Registration Number: NL-OMON54259
• Lead Sponsor: Genmab

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 25

Inclusion Criteria

• Subject must be at least 18 years of age.
• Subject has histologically or cytologically confirmed diagnosis of stage 4
NSCLC with at least 1 prior line of systemic therapy containing an
anti-PD-1/PD-L1 monoclonal antibody (mAb). Subjects must have demonstrated
disease progression (PD) as defined by RECIST v1.1. For the subjects whose most
recent anti-cancer therapy contained an anti-PD-1/PD-L1 mAb, their recent
evidence of PD must be confirmed by a second assessment no less than 4 weeks
from the date of the initial documented PD.
Note: Subject must have received at least 2 doses of an approved anti
PD-1/PD-L1 mAb approved in NSCLC.

o Subject has progressed during or after treatment with 1 anti-PD-1/PD-L1 mAb
administered either as monotherapy, or as SOC combination (subjects who have
received only anti-PD-1/PD-L1 mAb monotherapy as first-line therapy, are
eligible for this study if the investigator determines treatment with
platinum-containing chemotherapy is not appropriate, in line with local
treatment guidelines) or;
o Subject has progressed during or after platinum doublet chemotherapy
following an anti-PD-1/PD-L1 mAb or;
o Subject has progressed during or after an anti-PD-1/PD-L1 following platinum
doublet chemotherapy.

• Subject must have a tumor PD-L1 expression result available prior to C1D1
demonstrating PD-L1 expression in >=1% of tumor cells as assessed by a sponsor
designated central laboratory using the Dako PD-L1 IHC 22C3 pharmDx assay
(TPS>=1%), or per site local assessment with the Dako PD-L1 IHC 22C3 pharmDx
assay (TPS>=1%) or the VENTANA PD-L1 (SP263) assay (TC >=1%) adhering to the
manufacturer*s instructions.
Note: Local PD-L1 result needs to be performed on fresh tumor tissue (obtained
within 3 months prior to enrollment and after failure/stop of last prior
treatment) or, if not feasible, archival tissue (obtained within 12 months
prior to enrollment).
• Subject must have measurable disease per RECIST v1.1 as assessed by the
investigator.
• Subject must have ECOG PS <=1.
• Subject must have life expectancy of at least 3 months.
• Subject must have adequate organ and bone marrow function as described in the
protocol.

Exclusion Criteria

• Documentation of known EGFR sensitizing mutations, KRAS, RET, ROS1, BRAF
mutations, NTRK gene infusions, RET rearrangement, ALK gene rearrangements,
high level
MET amplification, or METex 14 skipping. If documentation of mutation status is
not available, for subjects with non-squamous histology or a mixed histology of
non-squamous and squamous, a formalin-fixed, paraffin-embedded tumor tissue
should be tested for biomarker panel analysis (which may include, but is not
limited to, EGFR, ALK, ROS1, BRAF, KRAS mutations, RET rearrangement, or NTRK
gene infusions, etc.). Subjects must not be randomized until biomarker status
is available in source
documentation at the site.
Note: Subjects with tumors harboring such targetable mutations, gene
rearrangements, or gene amplifications as described above may enroll in the
trial, if such subjects have also received an approved targeted therapy for
this indication assuming satisfactory fulfilment of all other eligibility
criteria (especially, at least 1 prior line of systemic therapy
containing an anti-PD-1/PD-L1 mAb for metastatic NSCLC disease).

• Subject has been exposed to any of the following prior therapies:
o Prior treatment with docetaxel for NSCLC.
o Prior treatment with a 4-1BB (CD137) targeted agent, any type of antitumor
vaccine, or autologous cell immunotherapy.
o Treatment with an anti-cancer agent within 28 days prior to GEN1046
administration.
• Subject discontinued treatment due to disease progression within the first 6
weeks of a CPI-containing treatment.

Study & Design

• Study Type: Interventional
• Study Design: Not specified