Advanced Solid Tumor
Conditions
Keywords
Malignant solid tumors, Immunotherapy, Standard of care (SoC) treatment, Clear cell renal cell carcinoma (ccRCC), Human epidermal growth factor receptor 2 (HER2) negative, Gastric cancer (GGC), Gastroesophageal junction cancer (GEJC), Non-small cell lung cancer (NSCLC), Actionable genomic alteration (AGA)- negative
Brief summary
This is a first-in-human (FIH), open-label, multi-site study which will evaluate the safety, efficacy, tolerability, pharmacokinetics (PK), and immunogenicity of increasing doses of BNT317 in participants with advanced solid tumors.
Detailed description
The study will consist of four parts, Part A, Part B1, Part B2 and Part B3. Part A will be a dose escalation part to investigate the safety and tolerability of BNT317 in participants with advanced solid tumors and may enroll additional participants with advanced solid tumors to specific dose levels (DLs), based on the emerging safety, PK, and pharmacodynamic data. Part A will evaluate up to six DLs of BNT317 monotherapy. Part B will include dose optimization and dose expansion components to further investigate the safety and tolerability of BNT317 and to investigate preliminary antitumor activity, i.e.: * Part B1 will further evaluate BNT317 monotherapy in participants with second-line of therapy or higher (2L+) clear cell renal cell carcinoma (ccRCC). Participants will be randomized 1:1 into two dose groups which will evaluate two DLs (as selected from Part A). * Part B2 will further evaluate BNT317 when added to standard of care (SoC) treatment in participants with 2L+ human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC)/gastroesophageal junction cancer (GEJC). Participants will be randomized 1:1 into two dose groups which will evaluate two DLs (as selected from Part A). * Part B3 will further evaluate BNT317 when added to SoC treatment in participants with 2L+ actionable genomic alteration (AGA)-negative non-small cell lung cancer (NSCLC) at the higher of the two BNT317 dose groups being investigated in Parts B1 and B2. Participants may receive investigational medicinal product (IMP) for up to 2 years or until they experience disease progression, unacceptable toxicities, withdrawal of consent, study discontinuation or investigator decision. The total duration of the study for a single participant may be up to 2 years, plus follow-up until the last participant has completed 1 year of survival follow-up (excluding screening). In Part A (dose escalation), an accelerated titration design for DL1 and a Bayesian Optimal Interval (BOIN) design for dose groups DL2 and above will be used to evaluate dose limiting toxicities (DLTs). Additional dosing schedules and/or intermediate or higher DLs may be evaluated based on the available safety, antitumor activity, PK, and pharmacodynamic data.
Interventions
BIOLOGICALBNT317 DL1
Intravenous infusion
BIOLOGICALBNT317 DL2
Intravenous infusion
BIOLOGICALBNT317 DL3
Intravenous infusion
BIOLOGICALBNT317 DL4
Intravenous infusion
BIOLOGICALBNT317 DL5
Intravenous infusion
BIOLOGICALBNT317 DL6
Intravenous infusion
BIOLOGICALBNT317 selected DLA
Intravenous infusion
BIOLOGICALBNT317 selected DLB
Intravenous infusion
DRUGSoC chemotherapy 1
Intravenous infusion
DRUGSoC chemotherapy 2
Intravenous infusion
Sponsors
BioNTech SE
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
If not specified otherwise, criteria listed below are applicable for all parts. Key Inclusion Criteria: * Have histologically or cytologically confirmed advanced tumors, who have failed standard therapy, or for whom no standard treatment option is available, or for whom standard therapy is not appropriate. * Have at least one measurable lesion based on RECIST v1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system \[CNS\] metastasis should not be considered as a measurable lesion). * Adequate hematologic and organ function, as defined in the protocol. * Have had an adequate treatment washout period before randomization/enrollment, as defined in the protocol. * Part B1 only: Histologically confirmed diagnosis of locally advanced, unresectable (not amenable to curative surgery or radiation therapy) or metastatic clear cell RCC (including those with sarcomatoid features). * Part B1 2L subgroup only: Had disease progression during or after one line of prior anticancer therapy for recurrent/metastatic disease which must have included immune checkpoint inhibitor and/or tyrosine kinase inhibitor (TKI). * Part B1 3L+ subgroup only: Had disease progression during or after two or more lines of prior anticancer therapy for recurrent/metastatic disease defined as the following: a. Prior treatment should also contain one or two of the following treatments: * One line of immune checkpoint inhibitor. * At least one line of a TKI. * Part B2 only: Undergoing SoC treatment or is willing to start SoC treatment for 2L+ HER2-negative GC/GEJC in accordance with the product label and local treatment guidelines. * Part B2 only: Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: Esophageal squamous cell carcinoma is excluded). * Part B2 2L subgroup only: Had disease progression during or after one prior line of anticancer therapy for recurrent/metastatic disease which must have included a fluoropyrimidine analogue and a platinum agent with or without programmed death (PD)-1/ PD-ligand 1 (PD-L1). The total of cytotoxic containing regimens must be limited to maximum of 1 line for the recurrent/metastatic setting. * Part B2 3L+ subgroup only: Had disease progression during or after two or more lines of prior anticancer therapy for recurrent/metastatic disease defined as the following: 1. Prior treatment must include one line of treatment containing a fluoropyrimidine analogue and a platinum agent, unless the participant is not a candidate in the opinion of the treating physician. 2. Prior treatment should also contain one or two of the following treatments: * One line of a cytotoxic agent per local SoC. * One line of a non-cytotoxic agent alone or in combination with cytotoxic chemotherapy. * Treatment with cytotoxic agents at the recurrent/metastatic setting must be limited to a maximum of two lines. * Part B2 only: Have a helicobacter pylori status result determined and documented prior to trial screening as part of SoC. * Part B3 only: Undergoing SoC treatment or is willing to start SoC treatment for 2L+ AGA-negative NSCLC in accordance with the product label and local treatment guidelines. * Part B3 only: Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC. * Part B3 only: Have no actionable genomic alterations, such as Epidermal Growth Factor Receptor mutations, anaplastic lymphoma kinase rearrangements, or other genomic alterations for which targeted molecular therapies are available. For enrolled participants with predominantly squamous histology tumors, molecular testing will not be required in cases where it is not part of the SoC. * Part B3 only: Have experienced relapse or progression during or after treatment with standard systemic therapy including platinum-based chemotherapy and/or immune checkpoint inhibitor in the advanced/metastatic setting or discontinued from prior therapy due to intolerance. * Part B3 only: Participants must have received 1 to 3 or more lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy (if PD-L1 positive), chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. Prior chemotherapy must be limited to 2 lines or less. Key
Exclusion criteria
* Have received any of the following therapies or drugs within the noted time intervals prior to study treatment: * Any prior treatment which inhibits cluster of differentiation 39. * Vaccination with live attenuated vaccine(s) within 4 weeks prior to the first dose of IMP. * Any investigational product within 4 weeks or 5 half lives (if the half life of the other investigational product is known), whichever is longer, before the first dose of IMP in this study or ongoing participation in the active treatment phase of another interventional clinical study. * Systemic cytotoxic chemotherapy, immunotherapy within 3 weeks or five half-lives of the chemotherapy (whichever is shorter) prior to the first dose of IMP. * Radiation therapy (chest, brain or internal organs) within 4 weeks prior to the first dose of IMP. * Palliative radiotherapy to metastasis within 2 weeks prior to the first dose of IMP. * Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 2 weeks prior to the first dose of IMP. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) is allowed. * Have any of the following CNS metastases: * Untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm). * Treated CNS metastases who are not neurologically stable or on steroids or anticonvulsants within 2 weeks before initiating IMP of this study. * Brain metastases treated with radiotherapy that are not confirmed stable by magnetic resonance imaging or contrast-enhanced computer tomography 4 weeks after radiotherapy. * Participants with known leptomeningeal metastases. * Have uncontrolled hypertension or poorly controlled diabetes as specified in the protocol. * Have a history of allogeneic hematopoietic stem cell transplantation or organ transplantation. * Have a history of serious Grade ≥3 immune-related adverse events (irAEs) or irAEs that led to discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to discontinuation of a prior immunotherapy may be included at the discretion of the investigator. If required by the investigator, after consultation with the sponsor. * Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A - Occurrence of DLTs | Up to 28 days after initiating BNT317 administration on Day 1 of Cycle 1 or the day before Cycle 3 Day 1, whichever comes earlier (each cycle is 14 days) | Per dose group. During the DLT observation period. |
| All parts - Occurrence of treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related adverse events (TRAEs), treatment-related Grade ≥3 TEAEs, and treatment-related SAEs | From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. |
| All parts - Occurrence of dose interruption, reductions, and discontinuation of BNT317 due to TEAEs | From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. |
| Parts B1, B2 & B3: Objective Response Rate (ORR) | From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A - ORR | From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. Defined as the proportion of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator's assessment) is observed as best overall response. |
| All parts - Duration of Response | From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. Defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first. |
| All parts - Disease Control Rate | From at least 6 weeks (±7 days) after the first BNT317 dose up to 100 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. Defined as the proportion of participants in whom a confirmed CR or PR or stable disease (per RECIST v1.1) is observed as best overall response per investigator's assessment. |
| All Parts - PK assessment: The maximum (peak) serum concentration (Cmax) of BNT317 | From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days) | Per dose group. If data permits. |
| All parts - PK assessment: Time to reach maximum (peak) serum concentration (Tmax) of BNT317 | From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days) | Per dose group. If data permits. |
| All parts - PK assessment: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time-curve (t1/2) of BNT317 | From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days) | Per dose group. If data permits. |
| All parts - PK assessment: The area under the curve (AUC) from time zero to infinity (AUCinf) of BNT317 | From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days) | Per dose group. If data permits. |
| All parts - PK assessment: The AUC from time zero to the end of the dosing period of BNT317 | From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days) | Per dose group. If data permits. |
| All parts - Anti-drug antibody (ADA) prevalence | From first dose of BNT317 up to 31 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. The proportion of participants who are ADA positive (either baseline or post-baseline). If data permits. |
| All parts - ADA incidence | From first dose of BNT317 up to 31 days after last dose of IMP or until a new anticancer therapy is initiated | Per dose group. The proportion of participants having treatment-emergent ADA). If data permits. |
Countries
Australia, United States
Contacts
CONTACTBioNTech clinical trials patient information
STUDY_DIRECTORBioNTech Responsible Person
BioNTech SE
Outcome results
None listed