Study of RO7515629 in Participants With HLA-G Positive Solid Tumors

• ClinicalTrials.gov Identifier: NCT05769959
• Recruitment Status: Terminated
• First Posted: March 15, 2023
• Last Update Posted: April 22, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 3, 2023
• First Posted Date: March 15, 2023
• Last Update Posted Date: April 22, 2024
• Actual Study Start Date: June 15, 2023
• Actual Primary Completion Date: March 19, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 3, 2023)

• Part 1, 2, 3: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 15 months ]
• Part 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: From start of study treatment (cycle 0 day -7 or cycle 0 day -14) until two weeks after second or third RO7515629 infusion (cycle 1 day 1) for a total DLT window of up to 28 days. ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 3, 2023)

• Part 1, 2, 3: Pharmacokinetic Analysis: Maximum Serum Concentration (Cmax) of RO7515629 [ Time Frame: Up to 13 months ]
• Part 1, 2, 3: Pharmacokinetic Analysis: Time of Maximum Serum Concentration (Tmax) of RO7515629 [ Time Frame: Up to 13 months ]
• Part 1, 2, 3: Pharmacokinetic Analysis: Minimum Serum Concentration (Cmin) of RO7515629 [ Time Frame: Up to 13 months ]
• Parts 1, 2, 3: Pharmacokinetic Analysis: Clearance (CL) of RO7515629 [ Time Frame: Up to 13 months ]
• Part 1, 2, 3: Pharmacokinetic Analysis: Volume of Distribution at Steady State (Vss) of RO7515629 [ Time Frame: Up to 13 months ]
• Part 1, 2, 3: Pharmacokinetic Analysis: Area Under The Curve (AUC) of RO7515629 [ Time Frame: Up to 13 months ]
• Part 1, 2, 3: Number of Participants With RO7515629 Anti-drug Antibodies (ADAs) [ Time Frame: Up to 13 months ]
• Part 1, 2, 3: Objective Response Rate (ORR) [ Time Frame: Up to approximately 18 months ]
• Part 1, 2, 3: Disease Control Rate (DCR) [ Time Frame: Up to approximately 18 months ]
• Part 1, 2, 3: Duration of Response (DoR) [ Time Frame: Up to approximately 18 months ]
• Part 1, 2, 3: Progression Free Survival (PFS) [ Time Frame: Up to approximately 18 months ]
• Part 1, 2, 3: Overall survival (OS) [ Time Frame: Up to approximately 18 months ]
  Defined as the time from first dose of study treatment to time of death.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of RO7515629 in Participants With HLA-G Positive Solid Tumors
• Official Title: An Open-Label, Multicenter, Phase 1 Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-Tumor Activity of RO7515629 in Participants With Unresectable and/or Metastatic HLA-G Positive Solid Tumors
• Brief Summary: The main purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, immune response and preliminary anti-tumor activity of RO7515629 alone in participants with advanced or metastatic solid tumors expressing human leukocyte antigen G (HLA-G).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Renal Cell Carcinoma
• Non-small Cell Lung Cancer
• Pancreatic Adenocarcinoma
• Colorectal Cancer
• Ovarian Neoplasms

Intervention

• Drug: RO7515629
  RO7515629 will be administered intravenously at a dose and schedule as specified for the respective study part and cohort.
• Drug: tocilizumab
  Tocilizumab will be used as rescue medication only. Tocilizumab will be administered as required for the management of cytokine release syndrome (CRS).
  Other Name: Actemra, RoActemra

Study Arms

• Experimental: Part I Single Participant Cohort RO7515629 Dose Escalation
  Participants will receive a fixed dose of RO7515629 intravenously as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
  Interventions:

  • Drug: RO7515629
  • Drug: tocilizumab
• Experimental: Part II Multiple Participant Cohort RO7515629 Dose Escalation
  Participants will receive RO7515629 intravenously, as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. In case of toxicity, step up dosing (single or double) may be implemented. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
  Interventions:

  • Drug: RO7515629
  • Drug: tocilizumab
• Experimental: Part III Multiple Participant Cohort RO7515629 Dose Expansion
  Participants with selected solid tumors will receive a selected dose of RO7515629 intravenously as a single agent based on the recommended dose sequence for expansion (RDE) and dosing regimen selected from Part I and Part II. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
  Interventions:

  • Drug: RO7515629
  • Drug: tocilizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 18, 2024): 3
• Original Estimated Enrollment (submitted: March 3, 2023): 150
• Actual Study Completion Date: March 19, 2024
• Actual Primary Completion Date: March 19, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Unresectable and/or metastatic HLA-G-positive solid tumors, for which standard therapy does not exist, or has proven to be ineffective or intolerable
• Confirmed HLA-G tumor expression.
• Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematological, liver, renal and pulmonary function
• Willingness to abide by protocol defined contraceptive requirements for the duration of the study.

Exclusion Criteria:

• History or clinical evidence of Central Nervous System (CNS) metastases unless protocol specified criteria are met
• Leptomeningeal metastases
• Rapid disease progression including lesions that are a threat to vital organs or non-irradiated lesions 2cm or larger at critical sites where tumor swelling may pose a risk to critical anatomical structures
• Participants with another invasive malignancy in the last 2 years unless protocol specified criteria are met
• Uncontrolled hypertension
• Active interstitial lung disease (ILD), pneumonitis or a history of ILD/pneumonitis requiring treatment with steroids, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan
• Participants with central cavitation or tumor(s) shown to be invading or abutting major blood vessels by imaging or the Investigator determines the tumor(s) is likely to invade major blood vessels and cause fatal bleeding
• Participants with pulmonary military metastatic pattern or pulmonary lymphangitic carcinomatosis
• History of pulmonary embolism within 3 months prior to study entry
• Significant cardiovascular disease
• Presence of active or uncontrolled infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to initiation of study treatment.
• Known hepatitis B or C (actively replicating) based on protocol specified criteria
• Known Human Immunodeficiency Virus (HIV) positivity
• Presence of an indwelling line or drain
• Active auto-immune disease that has required systemic therapy within the past 2 years unless protocol specified exceptions are met
• Major surgery within 28 days prior to first study treatment
• Last treatment with anti-cancer therapy or any investigational drug 28 days or less prior to the first study treatment
• Last dose of immunostimulating or immunosuppressive therapy 28 days or less prior to the first study treatment
• Regular dose of corticosteroids that exceeds prednisone 10 mg/day or equivalent within 28 days prior to first study treatment
• Prior treatment with T cell engaging or adoptive cell therapy
• Administration of a live, attenuated vaccine 28 days or less prior to first study treatment
• Contraindication or known hypersensitivity to any of the components of RO7515629 or tocilizumab or dexamethasone

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05769959
• Other Study ID Numbers: BP44068
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: April 2024