Solid Tumor, Adult
Conditions
Keywords
Cancer, Advanced cancer, Phase I, Metastatic cancer
Brief summary
The main purpose of this first-in-human study of GEN1056, is to evaluate safety. In addition, the study will determine the recommended dose and frequency for subsequent clinical studies and will assess the preliminary anti-tumor activity of GEN1056. GEN1056 will be studied in patients with advanced or metastatic solid cancer, for whom standard of care (SOC) therapy is not an option. All participants will get GEN1056.
Detailed description
The trial is a first-in-human open-label, dose-finding, multinational safety trial, in participants with advanced or metastatic solid (non central nervous system \[CNS\]) tumors that have exhausted SOC therapy or are not candidates for SOC therapy, evaluating the safety, tolerability, preliminary antitumor activity, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of GEN1056. The trial will be conducted as follows: * The Dose Escalation part (Part 1) will explore the safety of escalating doses of GEN1056 * The Dose schedule optimization part (Part 2) will explore further safety and tolerability in an alternate schedule of a dose based on data outcome available from Part 1.
Interventions
BIOLOGICALGEN1056
GEN1056 will be administered as an intravenous (IV) infusion. The dose levels will be determined by the starting dose and the escalation steps taken in the trial in Part 1. In Part 2, the dose and schedule will be decided based on data outcome from Part 1.
Sponsors
BioNTech SE
Genmab
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Subjects with histologically or cytologically confirmed non-CNS advanced or metastatic solid tumors which has progressed despite standard therapy, or subjects who are intolerant of standard therapy, or for which no standard therapy exists, and for whom, in the opinion of the investigator, experimental therapy with GEN1056 may be beneficial * Have personally (or in countries where permitted, their legally acceptable representative) signed an Informed Consent Form (ICF) * Are at least 18 years of age. * Have measurable disease according to the RECIST v1.1 criteria. * Have an ECOG PS of 0 to 1 at screening and on C1D1 pre-treatment. * Have acceptable laboratory test results during the screening period. * Must provide an archival (FFPE) tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. * A female subject with reproductive potential must agree to use adequate contraception during the trial, and for 4 months after receiving the last dose of trial drug GEN1056. Key
Exclusion criteria
* Subject is considered a poor medical risk due to a serious, uncontrolled inter-current illness * Prior therapy with a checkpoint inhibitor agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. * Prior exposure to any of the following prior therapies within the specified timeframes: 1. Systemic cytotoxic chemotherapy or antineoplastic biological therapy within 28 days or at least 5 elimination half-lives of the drug (whichever is shorter) of the first dose of trial treatment 2. Radiotherapy within 21 days of start of trial treatment. Note: palliative radiotherapy be allowed. 3. Prior treatment with live, attenuated vaccines within 28 days prior to initiation of GEN1056 * Known active CNS metastases and/or carcinomatous meningitis, or spinal cord compression. * Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen (HBsAg), HBV DNA), or Hepatitis C infection (Hepatitis C Virus Ribonucleic Acid (HCV RNA), HCV antibodies). * An active, known, or suspected autoimmune disease, requiring systemic steroid. * A condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. * History of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease requiring treatment with steroids. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | DLTs are evaluated during the first 21 days after a patient's first dose | To define the maximum tolerated dose (MTD) and/or recommended phase 2 dose(s) (RP2D) of GEN1056 |
| Incidence and severity of adverse events (AEs) | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Number of participants with clinical significant shifts from baseline in clinical laboratory parameters | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | Clinical laboratory parameters assessed: Hematology, biochemistry, coagulation, TSH, T3 and T4, urinalysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | From first infusion of trial drug to death due to any cause, or to last contact date in case of no observed death (assessed up to 2 years after the last participant's first dose in the trial) | Defined as time of death, due to any cause |
| Rate at which the drug is removed from the body (clearance) | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Amount of drug in the body (volume of distribution) | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Area under the concentration time curve (AUC) from time zero to last quantifiable sample AUClast | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Objective response rate (ORR) | From first infusion of trial drug to the last evaluable imaging assessment (an estimated average of 7 months) | Anti-tumor activity of GEN1056 as monotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for responders (with confirmation) |
| Time to reach maximum (peak) serum drug concentration (Tmax) after dosing | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Time after dosing at which the lowest drug concentration is observed before the next dose is administered, predose trough concentration (Ctrough) | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Elimination half-life (T1/2) of the drug | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Incidence of anti-drug antibodies (anti GEN1056 antibodies) | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | Characterize the immunogenicity of GEN1056 |
| Maximum (peak) observed serum drug concentration (Cmax) | Throughout the trial until the end of the safety follow-up period (90 days after last dose) | — |
| Duration of response (DOR) | From initial onset of response to first progression event (defined as radiographic progression or death; an estimated average of 7 months) | Anti-tumor activity of GEN1056 as monotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for responders (with confirmation) |
| Progression-free survival (PFS) | From first infusion of trial drug to first progression event (defined as radiographic progression or death; an estimated average of 7 months) | Anti-tumor activity of GEN1056 as monotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |
Countries
Georgia, Moldova, Spain
Outcome results
None listed