A Phase Ib/II, Multi-site, Open-label, Dose Finding Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of BNT326 in Combination With BNT327 in Participants With Advanced Non-small Cell Lung Cancer (NSCLC)
Study Identifier:
BNT326-02
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
Considering participating in a START clinical trial?
Study Summary
This is a multi-site, open-label, dose-finding study, consisting of Parts 1, 2a, and 2b to investigate the combination of BNT326 with BNT327 in participants with relapsed, progressive as well as treatment-naïve, advanced/metastatic non-small cell lung cancer (NSCLC).
This study will enroll adult participants with histologically or cytologically confirmed NSCLC that is advanced (i.e., either metastatic or recurrent tumors with no known curative treatment available).
Part 1: Determine the RP2D of BNT326 plus BNT327 by evaluating safety and tolerability in subjects with advanced NSCLC. Part 2a: Evaluate the safety profile and efficacy of BNT326 plus BNT327. Part 2b: Evaluate the efficacy of BNT326 plus BNT327 and determine its optimal dose.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
Read More
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified):
- Aged ≥18 years at the time of giving informed consent.
- Have measurable disease defined by RECIST v1.1.
- All participants have to provide a tumor tissue sample (e.g. Formalin-fixed paraffin-embedded [FFPE] slides or block) from archival tissue. Alternatively, a fresh biopsy should be collected, unless medically not justifiable to be conducted.
- Have Eastern Cooperative Oncology Group performance status of 0 or 1.
- Have adequate organ and bone marrow function within 7 days before randomization/enrollment.
- Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous (all cohorts) or only non-squamous (Cohort D2) NSCLC.
- Cohort-specific inclusion criteria
- Part 1, 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1
- for AGA-negative NSCLC only:
- Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase (ALK) gene rearrangements, or other genomic alterations for which targeted molecular therapies are available.
- Have experienced relapse or progression during or after treatment with standard systemic therapy in the advanced/metastatic setting or discontinued from prior therapy due to intolerance.
- Participants must have received 1 to 3 lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.
- for AGA-positive NSCLC only (excluding EGFR activating mutation):
- Have documented positive test results for one or more actionable genomic alteration: EGFR (other than activating mutations), ALK, ROS proto-oncogene 1 (ROS1), gene encoding the hepatocyte growth factor receptor (MET), human gene that encodes a protein called B-Raf (BRAF), rearranged during transfection (RET), neurotrophic tropomyosin-receptor kinase (NTRK), human epidermal growth factor receptor 2 (HER2), Kirsten rat sarcoma virus (KRAS), or other genomic alteration with available targeted therapy.
- Must have received at least one prior systemic therapy for advanced disease, which must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other alterations for which targeted therapies are available as a part of local SoC.
- Participants may have received between 1 to 3 lines of systemic treatment of anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents. These treatments may be administered concurrently (including with TKI) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.
- Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
- for AGA-positive NSCLC only (with EGFR activating mutation):
- Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
- Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.
- Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
- Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.
- Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
- Part 2a (Cohort A), 2L+, squamous or non-squamous NSCLC, AGA-negative/positive, any PD-L1
- for AGA-positive NSCLC only, excluding EGFR activating mutation:
- Have documented positive test results for one or more actionable genomic alterations: EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations, with available targeted therapy.
- May have received 1 to 4 lines of systemic treatment, of which one prior systemic therapy for advanced disease must have included targeted treatment for actionable genomic alterations, which include alterations such as EGFR (other than activating mutations), ALK, ROS1, MET, BRAF, RET, NTRK, HER2, KRAS, or other genomic alterations for which targeted therapies are available as part of local SoC.
- Other therapies may include anti-PD-1/PD-L1 therapy, chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently/in combination (including with TKI) or sequentially. However, chemotherapy treatment must be limited to 2 lines or less.
- Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
- for AGA-positive NSCLC only, with EGFR activation mutation:
- Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
- Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR TKI, with at least one being a third-generation EGFR TKI.
- Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
- Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.
- Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
- Part 2a (Cohort B), 1L, squamous or non-squamous NSCLC, AGA-negative, any PD-L1
- Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
- Have received no systemic anti-cancer treatment in the advanced/metastatic setting. May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 12 months after completing such therapy and have not received treatment in the advanced/metastatic setting.
- Part 2b (Cohort C), 2L+, squamous or non-squamous NSCLC, AGA-negative or EGFR activating mutation, any PD-L1
- for AGA-negative NSCLC only:
- Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
- Participants should have received 1 to 4 lines of systemic treatment, which can include anti-PD-1/PD-L1 therapy, chemotherapy, and/or anti-angiogenic agents.
- for EGFR-sensitizing mutation NSCLC only:
- Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del).
- Have received 1 or 2 prior systemic therapies for advanced and/or metastatic disease with an approved EGFR TKI, which must include one third-generation anti-EGFR TKI.
- Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1.
- Chemotherapy is permitted only if it was administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first line) treatment for advanced/metastatic disease.
- May have received neoadjuvant and/or adjuvant treatment if progression to advanced/metastatic disease occurred at least 6 months after completing such therapy and have experienced disease progression on or after EGFR TKI treatment administered in the advanced/metastatic setting.
- Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance.
- Part 2b (Cohort D1) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 ≥50% and Part 2b (Cohort D2) 1L, squamous or non-squamous NSCLC, AGA-negative, PD-L1 <50%
- Have no actionable genomic alterations, such as EGFR mutations, ALK rearrangements, or other genomic alterations for which targeted molecular therapies are available.
- Did not receive prior systemic therapy for advanced and/or metastatic disease.
Exclusion criteria
- Had disease progression on or were intolerant to prior treatment with an agent targeting HER3 (including antibody, ADC, cell therapy, and other drugs) or with a topoisomerase I inhibitor payload (including topoisomerase I inhibitor-containing ADCs). Note: For Part 2a Cohort A, prior exposure to agents targeting HER3 or topoisomerase I inhibitor payload may be allowed on a case-by-case basis after discussion with and approval by the sponsor.
- Have an uncontrolled concomitant or intercurrent illness, that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring AEs, including:
- Bleeding diathesis or active hemorrhage
- Active infection, including respiratory viral infection
- Child-Pugh class B or C cirrhosis
- Known pulmonary disease with significant impact in lung function and/or with potential risk of severe infection
- Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies)
- Psychiatric or abuse condition
- Colitis Grade ≥2 not resolved within 72 h within the past 3 months
- Have left ventricular ejection fraction <50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment.
- Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment.
- Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable.
- Have had exposure to protocol-specific treatments with a washout period before randomization/enrollment.
- Are participants of childbearing potential who are pregnant or breastfeeding or are planning pregnancy within the time specified in the protocol or are potentially fertile males, who are planning to father children during the study or within the time specified in the protocol.
- Are subject to exclusion periods from another investigational study.
- Have a history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP.
- Have urine protein ≥2+ and 24-hour urine protein excretion ≥1 g. If qualitative urine protein is ≤1+, a 24-hour urine protein quantitative test is not required.
- Have a history of Grade ≥3 immune-related adverse events that led to treatment discontinuation of a prior checkpoint inhibitor.
- Have clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
- Participants with significant risks of hemorrhage or evidence of major coagulation disorders.
- Have active or chronic corneal disorders or with any clinically significant corneal disease that prevents adequate monitoring of drug-induced keratopathy.
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.
Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Ramon Yarza
Status
Recruiting
Condition(s) Treated at Site
Non-Small Cell Lung Cancer