Trial to assess the safety and preliminary efficacy of GEN1055 on malignant solid tumors as monotherapy and as combination therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genmab A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Apr 2024 → 20 Nov 2025

Decision date (initial)

2024-03-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Genmab A/S

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Efficacy, Safety

Dose Escalation Phase 1a and 1b:
* Evaluate the safety of GEN1055 as monotherapy and as combination therapy with pembrolizumab
* Determine expansion doses of GEN1055 as monotherapy and as combination therapy with pembrolizumab

Expansion:
* Assess the antitumor activity of GEN1055 as monotherapy and as combination therapy

Secondary objectives 7

1. Dose Escalation Phase 1a and 1b: Characterize the PK properties of GEN1055 as monotherapy and as combination therapy with pembrolizumab
2. Dose Escalation Phase 1a and 1b: Evaluate immunogenicity of GEN1055
3. Dose Escalation Phase 1a and 1b: Assess the antitumor activity of GEN1055 as monotherapy and as combination therapy with pembrolizumab
4. Expansion: Assess the antitumor activity of GEN1055 as monotherapy and as combination therapy
5. Expansion: Evaluate safety of GEN1055 as monotherapy and as combination therapy
6. Expansion: Evaluate immunogenicity of GEN1055 as monotherapy and as combination therapy
7. Expansion: Characterize the PK of GEN1055 as monotherapy and in combination therapy

Conditions and MedDRA coding

Malignant Solid Tumors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Must sign an ICF indicating that the purpose of the trial and the procedures required for the trial are understood and indicating that the subject is willing to participate in the trial. Where required by local or country specific regulations, each subject must sign a separate ICF indicating agreement to provide samples for genomic biomarker analysis (DNA and RNA).
2. Is willing and able to adhere to the prohibitions and restrictions specified in this protocol.
3. Has acceptable laboratory test results prior to trial treatment, as follows: GFR GFR ≥45 mL/min/1.73 m2 according to the abbreviated MDRD equation: GFR = 186 × (SCr - 1.154) × (age - 0.203) × (0.742 if female), where SCr is expressed in mg/dL and the result is multiplied by 1.212 if the subject is black. ALT ≤3.0×ULN In case of a concomitant alkaline phosphatase level of >2.5×ULN, ALT and AST levels must be ≤1.5×ULN. AST ≤3.0×ULN Total bilirubin ≤1.5×ULN NOTE: A subject with Gilbert’s syndrome may be included if total bilirubin is ≤2×ULN and direct bilirubin is ≤1.5×ULN. Hemoglobin ≥9 g/dL (≥90 g/L or ≥5.6 mmol/L) NOTE: Red blood cell transfusion may be administered during Screening to meet this requirement unless subject is chronic transfusion dependent. Absolute neutrophil count >1.5×109/L (>1000/μL) NOTE: Must be met without administration of growth factors within 2 weeks prior to C1D1. Platelet count >100×109/L (>100,000/μL) NOTE: Must be met without administration of platelet transfusion within 2 weeks prior to C1D1.
4. Be at least 18 (or the legal age of consent in the jurisdiction in which the trial is taking place) years of age.
5. Have measurable disease according to RECIST v1.1.
6. Provide all pre-baseline scans since failure of last prior therapy (ie, documented radiographic PD), if available.
7. Have ECOG PS score of 0 to 1 at screening and on C1D1 pretreatment. Note: Do not perform C1D1 ECOG PS if within 3 days of Screening ECOG PS.
8. Provide a biopsy (ie, FFPE slides/block. A fresh biopsy taken during the screening period is preferred), unless medically unfeasible and reviewed and approved by the sponsor. If this cannot be provided, a biopsy taken after failure/stop of last prior treatment and taken within 6 months prior to C1D1 may be provided. Note: Documentation of biopsy collection and shipment must be submitted to the sponsor as a part of the eligibility package prior to administration of the first dose of trial treatment.
9. Additional for escalation part: Have histologically or cytologically confirmed non-CNS primary solid tumors and have metastatic or advanced disease.
10. Additional for escalation part: Criterion modified per Amendment 1: Have progressed on SoC therapy which should include platinum-based chemotherapy and anti-PD-1/PD-L1 therapies, if applicable for the tumor type,or for whom there is no available standard therapy likely to provide clinical benefit, and for whom experimental therapy with GEN1055 or GEN1055+pembrolizumab may be beneficial, in the opinion of the investigator.

Exclusion criteria 4

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 (including COVID-19 infection). * Significant cardiovascular impairment including i. Symptomatic congestive heart failure (Class III or IV as classified by the New York Heart Association), unstable angina pectoris, or cardiac arrhythmia. ii. Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management. iii. Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula. * Ongoing or recent (within 1 year of screening) 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. A subject with irAEs below grade 3 that led to discontinuation should be discussed with the sponsor. Grade 3 irAEs that have fully recovered may also be discussed. * History of chronic liver disease (eg, alcoholic hepatitis or NASH), drug-related or autoimmune hepatitis, or evidence of hepatic cirrhosis. * Evidence of interstitial lung disease. * Ongoing pneumonitis (any grade) including any radiological change of ongoing pneumonitis at baseline or history of noninfectious drug-, immune-, or radiation-related pneumonitis that has required steroids.
2. Hepatitis (testing for hepatitis B or C is not required unless mandated by local health authority): a. HBV: Has a medical history or positive serology for HBV (defined as positive for HBsAg or HBV DNA). • Above is not exclusionary if deemed due to vaccination, resolved natural infection, or passive immunization due to immunoglobulin therapy. b. HCV: Known active HCV infection (defined as positive for HCV RNA [qualitative]).
3. Has been exposed to any of the following prior therapies/treatments within the specified timeframes: * Treatment with an anticancer agent within 4 weeks or for systemic therapies within 5 half-lives of the drug, whichever is shorter, prior to trial treatment administration. * 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. * Has received G CSF/GM-CSF support within 2 weeks prior to first trial treatment administration or is chronically transfusion-dependent. * RT within 14 days before the planned first dose of trial treatment. Palliative RT of bone metastases up to 7 days prior to C1D1 will be allowed.
4. Has contraindications to the use of pembrolizumab, pemetrexed, paclitaxel, nab-paclitaxel, gemcitabine, cisplatin or carboplatin per local prescribing information as applicable for the planned trial treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose Escalation Phase 1a and 1b: Incidence and severity of AEs
2. Dose Escalation Phase 1a and 1b: Incidence of DLTs
3. Expansion: According to RECIST v1.1 as assessed by investigator: ORR

Secondary endpoints 8

1. Dose Escalation Phase 1a and 1b: PK parameters for GEN1055: • Cmax • tmax • Ctrough • AUC0-tlast • AUC0-inf • t½ • CL
2. Dose Escalation Phase 1a and 1b: ADA response to GEN1055 as monotherapy and as combination therapy with pembrolizumab
3. Dose Escalation Phase 1a and 1b: According to RECIST v1.1 as assessed by investigator: • ORR • DoR • TTR • DCR
4. Expansion: According to RECIST v1.1 as assessed by investigator: • DoR • TTR • DCR
5. Expansion: • PFS according to RECIST v1.1 as assessed by investigator • OS
6. Expansion: Incidence and severity of AEs
7. Expansion: ADA response to GEN1055 as monotherapy and as combination therapy
8. Expansion: PK parameters for GEN1055: • Cmax • tmax • Ctrough • AUC0-tlast • AUC0-inf • t½ • CL

Investigational products

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

Test 2

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genmab A/S

Sponsor organisation

Genmab A/S

Address

Carl Jacobsens Vej 30

City

Valby

Postcode

2500

Country

Denmark

Scientific contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Public contact point

Organisation

Genmab A/S

Contact name

Genmab Trial Information

Third parties 12

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

Documents 7 files

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

Application history

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