Clinical Trial 23673

• Overview

  Study Title:

  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)

  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).

  Objective:

  Primary Objectives *To determine the RP2D of BNT326 in combination with BNT327 by assessing the safety and tolerability in participants with advanced NSCLC. *To assess the safety profile of BNT326 in combination with BNT327. To assess the efficacy and determine the optimized dose of BNT326 in combination with BNT327. Secondary Objectives: *To evaluate the efficacy of BNT326 in combination with BNT327. *To evaluate the efficacy (other than ORR) of BNT326 in combination with BNT327 *To assess the safety profile of BNT326 in combination with BNT327. *To assess the PK of BNT326 (BNT326 ADC, total anti-HER3 antibody component, and unconjugated payload YL0010014 component) in combination therapy with BNT327. *To evaluate immunogenicity of BNT326 in combination therapy with BNT327.

• Treatments

  Therapies:

  Chemotherapy (NOS); HER3-targeting antibody-drug conjugate (ADC); Immunotherapy; Recombinant bispecific antibody targeting PD-L1 and VEGF; Topoisomerase I inhibitor

  Medications:

  Alimta (Pemetrexed); BNT326 (); BNT327 (); Paraplatin (carboplatin); Pembrolizumab (Keytruda); Pemetrexed (); Taxol (paclitaxel); carboplatin (); paclitaxel ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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.
  • Other protocol defined Inclusion/Exclusion criteria may apply.

• Exclusion Criteria

  Key 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.
  • Have left ventricular ejection fraction > 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.
  • Other protocol defined Inclusion/Exclusion criteria may apply.

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