A Study to Evaluate Safety, Tolerability, and Preliminary Effect of the GEN1053 Antibody on Malignant Solid Tumors as Monotherapy and in Combination

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab B.V., Genmab B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Nov 2022 → 24 May 2024

Decision date (initial)

2023-01-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genmab

External identifiers

EU CT number

2022-502419-12-00

EudraCT number

2021-006692-42

ClinicalTrials.gov

NCT05435339

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Pharmacodynamic

•Determine MTD/MAD/RP2Ds of GEN1053 as monotherapy and in combination with immunomodulator
•Establish initial safety profile of GEN1053 as monotherapy and in combination with immunomodulator

Secondary objectives 3

1. Establish pharmacokinetic (PK) profile of GEN1053 as monotherapy and in combination with immunomodulator
2. Evaluate immunogenicity of GEN1053 as monotherapy and in combination with immunomodulator
3. Evaluate antitumor activity of GEN1053 as monotherapy and in combination with immunomodulator

Conditions and MedDRA coding

Malignant Solid Tumors

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. For both the Dose Escalation and Expansion parts: Subject must: •Be ≥18 years of age.
2. •Have measurable disease according to RECIST 1.1
3. •Provide all pre-baseline scans since failure of last prior therapy (ie documented radiographic PD), if available
4. •Have Eastern Cooperative Oncology Group performance status ≤1.
5. •Have organ and bone marrow function as follows: Bone marrow / hematological function: ▪Absolute neutrophil count (ANC) ≥1.5×109/L ▪Hemoglobin ≥9.0 g/dL ▪Platelet count ≥150×109/L Liver function: ▪Total bilirubin ≤ upper limit of normal (ULN) ▪Alanine aminotransferase ≤1.5×ULN ▪Aspartate aminotransferase ≤1.5×ULN ▪Albumin ≥30 g/L Coagulation status: ▪Prothrombin time (PT)/International normalized ratio ≤1.5 ▪Activated partial thromboplastin time (aPTT) ≤1.5×ULN Renal function: Glomerular filtration rate ≥45 mL/min/1.73 m², according to the abbreviated MDRD
6. For Monotherapy Dose Escalation (phase 1a) and Combination therapy Dose Escalation (phase 1b) only: •Subjects with histologically or cytologically confirmed non-CNS solid tumors that are metastatic or advanced.
7. •Subjects who have progressed on standard of care therapy or for whom there is no available standard therapy likely to provide clinical benefit, or who are not candidates for available therapy or who have previously refused available therapy, and for whom, experimental therapy with GEN1053 or GEN1053+IM may be beneficial, in the opinion of the investigator.
8. •Fresh biopsies mandatory for all patients in Monotherapy Dose Escalation and Combination therapy Dose Escalation
9. For the Expansion part Only: •Subjects with histologically or cytologically confirmed diagnosis of recurrent, unresectable or metastatic HNSCC or metastatic NSCLC, who do not have any further available standard therapy or who are not candidates for standard therapy or who have previously refused standard therapy (if subjects had access), and for whom experimental therapy with GEN1053 or GEN1053+IM may be beneficial, in the opinion of the investigator.

Exclusion criteria 2

1. •Has uncontrolled intercurrent illness, including but not limited to: -Ongoing or active infection requiring IV treatment with anti-infective therapy administered less than 2 weeks prior to first dose. -Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia. -Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management. -Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula. -Ongoing or recent (within 1 year) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs. -History of grade 3 or higher irAEs that led to treatment discontinuation of a CPI. -History of chronic liver disease or evidence of hepatic cirrhosis. -Evidence of interstitial lung disease. -Ongoing pneumonitis or history of non-infectious pneumonitis that has required steroids. -Known platelet function defects.
2. •Prior therapy: -Radiotherapy within 14 days prior to first GEN1053 administration. Palliative radiotherapy will be allowed. -Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1053 administration. -Subject with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal or pituitary replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Dose-limiting toxicities (DLTs; Dose Escalation parts only)
2. Adverse events (AEs) and safety laboratory parameters

Secondary endpoints 3

1. PK parameters: clearance, volume of distribution, maximum concentration, time of Cmax, predose trough concentrations, half-life, area under the concentration-time curve
2. Antidrug antibody response of GEN1053 and in combination with IM
3. Antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1: objective response rate (ORR), disease control rate (DCR), duration of response (DoR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genmab B.V.

Sponsor organisation

Genmab B.V.

Address

Uppsalalaan 15

City

Utrecht

Postcode

3584 CT

Country

Netherlands

Scientific contact point

Organisation

Genmab B.V.

Contact name

Genmab Trial Information

Public contact point

Organisation

Genmab B.V.

Contact name

Genmab Trial Information

Third parties 13

Genmab B.V.

Sponsor organisation

Genmab B.V.

Address

Uppsalalaan 15

City

Utrecht

Postcode

3584 CT

Country

Netherlands

Scientific contact point

Organisation

Genmab B.V.

Contact name

Genmab Trial Information

Public contact point

Organisation

Genmab B.V.

Contact name

Genmab Trial Information

Third parties 13

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications