Clinical trial NCT04857138: A Study to Evaluate Safety, Pharmacokinetics and Anti-Tumor Activity of RO7300490, as Single Agent or in Combination With Atezolizumab in Participants With Advanced Solid Tumors
Official title: An Open-Label, Multicenter, Dose-Escalation and Expansion, Phase I Study to Evaluate Safety, Pharmacokinetics, And Anti-Tumor Activity of RO7300490, A Fibroblast Activation Protein-α (FAP) Targeted CD40 Agonist, as Single Agent or in Combination With Atezolizumab in Participants With Advanced and/or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2021-04-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A study to evaluate the safety, pharmacokinetics and anti-tumor activity of RO7300490 as a single agent or in combination with atezolizumab. The study will consist of 3 parts: \[Part 1\] Dose-Escalation of RO7300490 as a single agent; \[Part 2\] Dose-Escalation of RO7300490 in combination with atezolizumab and \[Part 3\] Dose-Expansion of RO7300490 in combination with atezolizumab in selected cancer types.


Eligibility criteria: Inclusion Criteria:

* Life expectancy of \>= 12 weeks.
* Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors that are not amenable to standard therapy.
* Radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Agreement to provide protocol-specific biopsy material.
* Adverse Events (AEs) from prior anti-cancer therapy resolved to Grade =\<1.
* Adequate performance status and cardiovascular, hematological, liver, renal and coagulation function.
* For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs.
* For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm.

Exclusion Criteria:

* Known central nervous system (CNS) primary tumors or metastases, including leptomeningeal metastases, unless protocol-specific conditions are met.
* Active second invasive malignancy within two years prior to screening.
* Significant cardiovascular/cerebrovascular disease within 6 months prior to study treatment start.
* Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that gives reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.
* Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
* Active or history of autoimmune disease.
* Known hypersensitivity to any of the components of RO7300490 formulation or to components of atezolizumab formulation.
* Pregnancy, lactation or breastfeeding.
* Dementia or altered mental status that would prohibit informed consent.
* Major surgery or significant traumatic injury within 28 days prior to the first study drug administration (excluding biopsies) or anticipation of the need for major surgery during study treatment.
* Treatment with radiotherapy, chemotherapy, hormonal therapy, targeted therapy, immunotherapy or investigational drug concurrent or within 28 days or 5 half-lives of the drug (whichever is shorter) before the first study drug administration.

Primary outcomes:
measure: Percentage of Participants with Adverse Events (AEs) (Parts 1 and 2)
timeFrame: Up to 36 months
measure: Percentage of Participants with Dose-Limiting Toxicities (DLTs) (Parts 1 and 2)
timeFrame: Up to 36 months
measure: Objective Response Rate (ORR) (Part 3)
timeFrame: Up to 48 months
Secondary outcomes:
measure: Area Under The Curve (AUC) of RO7300490 (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Minimum Concentration (Cmin) of RO7300490 (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Maximum Concentration (Cmax) of RO7300490 (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Clearance (CL) of RO7300490 (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Volume of Distribution at Steady State (Vss) of RO7300490 (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Percentage of Participants with Anti-RO7300490 Antibodies (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Objective Response Rate (ORR) (Parts 1 and 2)
timeFrame: Up to 48 months
measure: Disease Control Rate (DCR) (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Duration of Response (DOR) (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Progression-Free Survival (PFS) On-Treatment (Parts 1, 2 and 3)
timeFrame: Up to 48 months
measure: Percentage of Participants With Adverse Events (AEs) (Part 3)
timeFrame: Up to 48 months
Other outcomes:
Locations:
city: København Ø
country: Denmark
facility: Rigshospitalet; Fase 1 Enhed - Onkologi
city: Villejuif
country: France
facility: Gustave Roussy
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de Oncologia
state: Navarra
city: Barcelona
country: Spain
facility: Vall d?Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra Madrid; Servicio de Oncología
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundacion Jimenez Diaz
city: Edinburgh
country: United Kingdom
facility: Western General Hospital; Edinburgh Cancer Center
city: London
country: United Kingdom
facility: Guys and St Thomas Hospital; OHCT Clinical Trials
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust; Experimental Cancer Medicine Team
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: