Trial to Assess the Safety and Preliminary Efficacy of GEN1055 on Malignant Solid Tumors as Monotherapy and as Combination Therapy
First-In-Human, Open-Label, Dose Escalation Trial With Expansion Cohorts to Evaluate the Safety and Preliminary Efficacy of GEN1055 as Monotherapy and as Combination Therapy in Subjects With Malignant Solid Tumors
The goal of this trial is to learn about the antibody GEN1055 when it is used alone and when it is used together with another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of participants with certain types of cancer. Participants will receive either GEN1055 alone, GEN1055 with pembrolizumab, or GEN1055 with pembrolizumab and chemotherapy. All participants will receive active drug; no one will receive placebo.
This trial has 2 parts. The purpose of the first part is to find out if GEN1055 is safe and to find out the doses of GEN1055 to use alone and to use with pembrolizumab. The purpose of the second part is to give GEN1055 to more participants to see how well the doses of GEN1055 that were selected in the first part work against cancer alone and how well they work with pembrolizumab (with or without other chemotherapy).
A participant will receive trial treatment up to a maximum of 24 months for pembrolizumab-containing regimens, or until:
- the cancer progresses.
- there are side effects requiring that treatment be stopped.
- the participant decides to not participate further in this trial.
- the doctor believes it is in the participant's best interest to stop treatment.
Participation in the trial will require visits to the site. For the first 12 weeks there will be weekly visits and after that, visits will be every 3 weeks. At site visits, there will be various tests (such as blood draws) and procedures (such as recording of heart activity, computed tomography (CT) scans) to monitor whether the treatment is safe and effective. The trial duration (including screening, treatment, and follow-up) for each participant will be about 39 months.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a multi-center trial and will be conducted in two parts: dose escalation (phase 1a/1b) and expansion (phase 2a).
The Dose Escalation part of the trial will evaluate dose-limiting toxicities (DLTs) to determine the recommended phase 2 dose (RP2D), and if reached, the maximum tolerated dose (MTD) in participants with locally advanced or metastatic solid tumors.
The Expansion part will evaluate safety, tolerability, mechanism of action (MoA), immunogenicity, pharmacokinetic (PK), and initial antitumor activity of the selected doses and schedules in selected tumor indications.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Barcelona, Spain
- Hospital Universtari Val D´Hebron
-
Madrid, Spain
- Start Madrid Ciocc Hm Sanchinarro
-
Pamplona, Spain, 31008
- Clinica Universidad de Navarra
-
-
-
-
Connecticut
-
New Haven, Connecticut, United States, 06510
- Yale-New Haven Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
All cohorts:
- Be at least 18 years of age.
- Have measurable disease according to RECIST v1.1.
- Provide all pre-baseline scans since failure of last prior therapy (ie, documented radiographic progressive disease [PD]), if available.
- Have Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 to 1 at screening and on C1D1 pretreatment.
- Provide a biopsy (ie, formalin-fixed paraffin-embedded slides/block). A fresh biopsy taken during the screening period is preferred, unless medically unfeasible and after review and approval 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.
Phase 1a and 1b- Dose Escalation:
- Have histologically or cytologically confirmed non-Central Nervous System (CNS) primary solid tumors who have metastatic or advanced disease.
- Have progressed on standard of care (SoC) therapy which should include platinum-based chemotherapy and anti-PD/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.
Phase 2a - Expansion:
Inclusion criteria specific to selected tumor indications may apply.
Exclusion Criteria:
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 coronavirus disease 2019 [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-millimeter (mm) Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management.
iii) Prolonged corrected QT 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 immune-related adverse events (irAEs).
- History of grade 3 or higher irAEs that led to treatment discontinuation of a checkpoint inhibitor (CPI). A participant 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 nonalcoholic steatohepatitis), 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.
- 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 granulocyte or granulocyte/macrophage colony-stimulating factor 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.
- Hepatitis (testing for hepatitis B or C is not required unless mandated by local health authority):
Hepatitis B virus (HBV): Has a medical history or positive serology for HBV (defined as positive for hepatitis B surface antigen or HBV deoxyribonucleic acid [DNA]).
i) Above is not exclusionary if deemed due to vaccination, resolved natural infection, or passive immunization due to immunoglobulin therapy.
- Hepatitis C virus (HCV): Known active HCV infection (defined as positive for HCV ribonucleic acid [RNA] [qualitative]).
Note: Other protocol defined inclusion and exclusion criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Dose Escalation
GEN1055 will be administered as monotherapy and in combination with a fixed dose of pembrolizumab.
|
Intravenous (IV) administration.
IV administration
|
|
Experimental: Expansion
GEN1055 will be administered as monotherapy or in combination with pembrolizumab or in combination with pembrolizumab and standard chemotherapy in separate expansion cohorts, at a dose level selected from the Dose Escalation part.
|
Intravenous (IV) administration.
IV administration
IV administration
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Dose Escalation: Number of Participants With Adverse Events (AEs)
Time Frame: Up to approximately 1.5 years
|
An AE was defined as any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
|
Up to approximately 1.5 years
|
|
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: 21 days
|
A DLT was defined as any of the following events during the DLT evaluation period (21 days).
All grade 5 events, anaphylaxis, grade ≥3 infusion-related reaction (IRR), hematological events (grade 4 neutropenia lasting more than 7 days, grade 4 thrombocytopenia for ≥7 consecutive days, grade 3/4 febrile neutropenia for more than 1 hour, grade 3/4 hemorrhage associated with thrombocytopenia of ≥ grade 3 requiring platelet transfusion, grade 4 anemia), nonhematological events (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] elevations ≥ grade 2 with concomitant bilirubin >2.0×upper limit of normal [ULN] with no signs of cholestasis and no other reason can be found to explain the combination of increased ALT/AST and total bilirubin, ie, a Hy's law case, all nonhematological toxicities of grade ≥3 (severe or life-threatening), with exclusions per protocol).
Toxicities were graded for severity according to National Cancer Institute Common Terminology Criteria
|
21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Dose Escalation: Maximum (Peak) Plasma Concentration (Cmax) of GEN1055
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
|
Blood samples were collected and processed to obtain plasma to evaluate the pharmacokinetics (PK) of GEN1055.
|
Cycle 1 and Cycle 2 (cycles were 21 days)
|
|
Dose Escalation: Time to Reach Cmax (Tmax) for GEN1055
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
|
Blood samples were collected and processed to obtain plasma, to evaluate the PK of GEN1055.
|
Cycle 1 and Cycle 2 (cycles were 21 days)
|
|
Dose Escalation: Plasma Trough (Pre-dose) Concentrations (Ctrough) of GEN1055
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
|
Blood samples were collected and processed to obtain plasma, to evaluate the PK of GEN1055.
|
Cycle 1 and Cycle 2 (cycles were 21 days)
|
|
Dose Escalation: Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Sample (AUC0-tlast) for GEN1055
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
|
Blood samples were collected and processed to obtain plasma, to evaluate the PK of GEN1055.
|
Cycle 1 and Cycle 2 (cycles were 21 days)
|
|
Dose Escalation: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) for GEN1055
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
|
Blood samples were collected and processed to obtain plasma, to evaluate the PK of GEN1055.
|
Cycle 1 and Cycle 2 (cycles were 21 days)
|
|
Dose Escalation: Half-life (t½) of GEN1055
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
|
Blood samples were collected and processed to obtain plasma, to evaluate the PK of GEN1055.
|
Cycle 1 and Cycle 2 (cycles were 21 days)
|
|
Dose Escalation: Clearance (CL) of GEN1055 From the Plasma
Time Frame: Cycle 1 and Cycle 2 (cycles were 21 days)
|
Blood samples were collected and processed to obtain plasma to evaluate the PK of GEN1055.
|
Cycle 1 and Cycle 2 (cycles were 21 days)
|
|
Dose Escalation: Number of Participants With Anti-Drug Antibodies (ADA)
Time Frame: Up to approximately 1.5 years
|
Venous blood samples were drawn for analysis of ADAs.
|
Up to approximately 1.5 years
|
|
Dose Escalation: Overall Response Rate (ORR)
Time Frame: Up to approximately 1.5 years
|
ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as assessed by investigator.
CR was defined as disappearance of all target and non-target tumor lesions, reduction in short axis to <10 millimeters (mm) in all pathological target and non-target lymph nodes and normalization of tumor marker level (if applicable).
PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
Up to approximately 1.5 years
|
|
Dose Escalation: Duration of Response (DOR)
Time Frame: Up to approximately 1.5 years
|
DOR based on investigator assessment was defined as the time from the first documentation of response (CR or PR) to the date of progressive disease (PD) or death, whichever occurred earlier according to RECIST v1.1. CR was defined as disappearance of all target and non-target tumor lesions, reduction in short axis to <10 mm in all pathological target and non-target lymph nodes and normalization of tumor marker level (if applicable). PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 1 of the following: ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute increase of ≥5 mm in the sum of diameters, or unequivocal appearance of 1 or more new lesion(s), or unequivocal progression of non-target lesions. |
Up to approximately 1.5 years
|
|
Dose Escalation: Time to Response (TTR)
Time Frame: Up to approximately 1.5 years
|
TTR based on investigator assessment was defined as the time from Cycle 1 Day 1 (C1D1) to first documentation of objective response (CR or PR) in participants achieving PR or CR according to RECIST v1.1.
CR was defined as disappearance of all target and non-target tumor lesions, reduction in short axis to <10 mm in all pathological target and non-target lymph nodes and normalization of tumor marker level (if applicable).
PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
Up to approximately 1.5 years
|
|
Dose Escalation: Disease Control Rate (DCR)
Time Frame: Up to approximately 1.5 years
|
DCR was defined as the percentage of participants with BOR of CR, PR, or stable disease (SD) according to RECIST v1.1 as assessed by investigator.
CR was defined as disappearance of all target and non-target tumor lesions, reduction in short axis to <10 mm in all pathological target and non-target lymph nodes and normalization of tumor marker level (if applicable).
PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters (nadir) while on trial.
|
Up to approximately 1.5 years
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GCT1055-01
- 2023-507049-28-00 (Ctis)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.