A First-in-human, Open-label, Multicenter Phase I/II Study to Evaluate the Safety and Anti-tumor Activity of ANV600 As Single Agent and in Combination with Pembrolizumab in Participants with Advanced Solid Tumors (EXPAND-1)
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Study Summary
To Evaluate the Safety and Anti-Tumor Activity of ANV600 as Single Agent and in Combination with Pembrolizumab in Participants with Relapsed/Refractory Advanced Solid Tumors
Phase I (dose escalation): To identify the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of ANV600 single agent and in combination with pembrolizumab.
Phase II: To assess the anti-tumor activity of ANV600 as single agent and in combination with pembrolizumab.
To characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and antitumor activity of ANV600 administered as a single agent or in combination with pembrolizumab in patients with advanced solid tumors.
The Phase I will determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of ANV600 administered intravenously every 2 weeks (Q2W) either as single agent or in combination with pembrolizumab in previously treated advanced solid tumors.
To determine the MTD and/or RP2D. Once the RP2D has been determined, ANV600 will be further evaluated as monotherapy and in combination with pembrolizumab in the Phase II part of the study for efficacy and safety in PD-1 experienced patients with advanced melanoma, NSCLC and HNSCC. Tumor response will be assessed using RECIST v1.1.
Phase II will evaluate efficacy and safety of ANV600 in tumor-specific expansion cohorts.
- * The participant provides written informed consent for the trial;
- * Life-expectancy ≥ 3 months;
- * Able to comply with the Protocol as judged by the Investigator;
- * ≥ 18 years of age on day of signing informed consent;
- * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
- * Measurable disease per RECIST v1.1;
- * Adequate organ function, defined as:
- * Absolute neutrophil count (ANC) ≥1200/µL;
- * Platelet count ≥100 000/µL;
- * Hemoglobin ≥9.0 g/dL;
- * Measured or calculated creatinine clearance ≥50 mL/min;
- * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases);
- * Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN;
- * Phase I: Advanced unresectable or metastatic solid tumors for which no standard of care treatments are available, or participants who cannot tolerate such treatment;
- * Phase II: Tumor-specific cohorts in adult participants with advanced solid tumors:
- * Cohort A: Unresectable Stage III or Stage IV cutaneous melanoma (excl. mucosal and uveal), which has progressed on/after treatment with a PD-1/L1 checkpoint inhibitor;
- * Cohort B: Unresectable or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC) not eligible for an approved targeted therapy, which has progressed on/after treatment with a PD-1/L1 checkpoint inhibitor;
- * Cohort C: Recurrent and/or unresectable/metastatic head and neck squamous cell carcinoma (HNSCC) (except nasopharyngeal carcinoma), after platinum failure and a PD-1/L1 checkpoint inhibitor.
- Additional inclusion criteria apply as per study protocol
- Exclusion criteria
- * Pancreatic cancer (e.g. PDAC) (Phase I only);
- * Primary or secondary adrenal insufficiency (Phase I only);
- * History of allergic reactions attributed to any of the excipients of ANV600, such as sucrose, histidine or polysorbate 80. For combination only: severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients;
- * Investigational agent (including investigational device) within 4 weeks or an interval of five half-lives of the respective investigational agent prior to study Day 1, whichever is shorter;
- * Received IL-2 or IL-2 analogues as anti-cancer therapy within 18 months prior to study Day 1 (except IL-2 given in combination with cell therapy [e.g. TILs]);
- * Not recovered (i.e. ≤ Grade 1 at baseline) from AEs resulting from prior immunotherapies with the following exceptions:
- 1. Autoimmune AEs controlled by replacement therapy (e.g., hypothyroidism, adrenal insufficiency)
- 2. Vitiligo or alopecia
- 3. Psoriasis;
- * Received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to treatment; Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
- * For combination only: Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher irAE;
- * Active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
- * Additional malignancy that is progressing or has required active treatment within the past 3 years;
- * Active autoimmune disease that has required systemic treatment in the past 2 years;
- * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug;
- * Allogeneic tissue/solid organ or stem cell transplant;
- * History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
- * Active infection requiring systemic therapy;
- Additional exclusion criteria apply per study protocol
Clinical Study Information for Healthcare Providers
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