Clinical trial NCT06470763: A Study Evaluating ANV600 Single Agent or in Combination with Pembrolizumab in Participants with Advanced Solid Tumors (EXPAND-1)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Anaveon AG
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-06-24
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of study ANV600-001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity and antitumor activity of ANV600 administered as a single agent or in combination with pembrolizumab in adult participants with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* 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

Primary outcomes:
measure: Phase I dose escalation: Incidence of Dose Limiting Toxicities (DLT) with ANV600 single agent and in combination with pembrolizumab combination with pembrolizumab
timeFrame: Day 1 up to 24 months
measure: Phase I dose escalation: Frequency and severity of treatment-emergent adverse events (TEAEs) with ANV600 and in combination with pembrolizumab
timeFrame: Day 1 up to 24 months
measure: Phase II: Objective Response Rate (ORR) using RECIST v1.1
timeFrame: Day 1 up to 24 months
measure: Phase II: Duration of Response (DOR) using RECIST v1.1
timeFrame: Day 1 up to 24 months
Secondary outcomes:
measure: Phase I Dose escalation: Serum concentration of ANV600 following a single dose and after repeated dosing
timeFrame: Day 1 up to 24 months
measure: Phase I Dose escalation: Immunogenicity as indicated by the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (nAb)
timeFrame: Day 1 up to 24 months
measure: Phase I Dose escalation: Objective response rate (ORR) using RECIST v1.1
timeFrame: Day 1 up to 24 months
measure: Phase I Dose escalation: Duration of response (DOR) using RECIST v1.1
timeFrame: Day 1 up to 24 months
measure: Phase II: Progression-free survival (PFS)
timeFrame: Day 1 up to 24 months
measure: Phase II: Overall Survival (OS)
timeFrame: Day 1 up to 24 months
measure: Phase II: Frequency and severity of treatment-emergent adverse events (TEAEs) with ANV600 and in combination with pembrolizumab
timeFrame: Day 1 up to 24 months
measure: Phase II: PK parameters based on ANV600 serum levels following a single dose and after repeated dosing
timeFrame: Day 1 up to 24 months
measure: Phase II: Immunogenicity as indicated by the incidence of antidrug antibodies (ADA) and neutralizing antibodies (nAb)
timeFrame: Day 1 up to 24 months
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bordeaux
country: France
facility: Institut Bergonie
city: Marseille
country: France
facility: CEPCM - AP-HM Hopital de la Timone
city: Toulouse
country: France
facility: Oncopole Claudius Regaud, Toulouse
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest - Institut für Klinisch-Onkologische Forschung (IKF)
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (VHIO)
city: Madrid
country: Spain
facility: START Madrid CIOCC
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
city: Valencia
country: Spain
facility: INCLIVA Foundation
city: Bellinzona
country: Switzerland
facility: Ente Ospedaliero Cantonale - Istituto Oncologico della Svizzera Italiana
city: St Gallen
country: Switzerland
facility: Cantonal Hospital St Gallen
Study officials:
References: