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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03708328




Registration number
NCT03708328
Ethics application status
Date submitted
9/10/2018
Date registered
17/10/2018

Titles & IDs
Public title
A Dose Escalation and Expansion Study of Lomvastomig, a PD-1/TIM-3 Bispecific Antibody, in Participants With Advanced and/or Metastatic Solid Tumors
Scientific title
An Open Label, Multicenter, Dose Escalation and Expansion, Phase 1 Study to Evaluate Safety, Pharmacokinetics, and Preliminary Anti-Tumor Activity of RO7121661, a PD-1/TIM-3 Bispecific Antibody, in Patients With Advanced and/or Metastatic Solid Tumors
Secondary ID [1] 0 0
2018-000982-35
Secondary ID [2] 0 0
NP40435
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 0 0
Metastatic Melanoma 0 0
Non-small Cell Lung Cancer (NSCLC) 0 0
Small Cell Lung Cancer (SCLC) 0 0
Esophageal Squamous Cell Carcinoma (ESCC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lomvastomig

Experimental: Dose Escalation Part A: Once Every 2 Weeks (Q2W) - Lomvastomig will be administered in treatment cycles once every 2 weeks (Q2W). Dose escalation will be carried out according to a modified continual reassessment method (mCRM) with escalation with overdose control (EWOC) design.

Experimental: Expansion Part B1: Metastatic Melanoma Cohort - This cohort will comprise participants with checkpoint inhibitor (CPI) experienced, second line and beyond metastatic melanoma. The starting dose of lomvastomig for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.

Experimental: Expansion Part B2: NSCLC Cohort 1 - This cohort will comprise participants with CPI and platinum experienced, second or third line PD-L1 positive non-small cell lung cancer (NSCLC). The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.

Experimental: Expansion Part B3: NSCLC Cohort 2 - This cohort will comprise participants with PD-L1 high, cancer immunotherapy (CIT) naïve first line NSCLC. The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.

Experimental: Expansion Part B4: SCLC Cohort - This cohort will comprise participants with CPI naïve small cell lung cancer (SCLC) with prior failure of, progression on, or intolerance to, standard therapy. The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.

Experimental: Expansion Part B5: ESCC Cohort - This cohort will comprise participants with CPI-naïve esophageal squamous cell carcinoma (ESCC). The starting dose of lomvastomig for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.


Treatment: Drugs: Lomvastomig
Lomvastomig will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation: Number of Participants with a Dose-Limiting Toxicity (DLT)
Timepoint [1] 0 0
For Part A (1 cycle is 14 days): From Cycle 1 Day 1 to Cycle 2 Day 7 (up to 35 days)
Primary outcome [2] 0 0
Dose Escalation: Number of Participants with at Least One Adverse Event, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Timepoint [2] 0 0
Up to 27 months
Primary outcome [3] 0 0
Expansion: Objective Response Rate, Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Timepoint [3] 0 0
Up to 27 months
Primary outcome [4] 0 0
Expansion: Disease Control Rate, Assessed According to RECIST v1.1
Timepoint [4] 0 0
Up to 27 months
Primary outcome [5] 0 0
Expansion: Duration of Response, Assessed According to RECIST v1.1
Timepoint [5] 0 0
Up to 27 months
Primary outcome [6] 0 0
Expansion: Progression Free Survival, Assessed According to RECIST v1.1
Timepoint [6] 0 0
Up to 27 months
Secondary outcome [1] 0 0
Dose Escalation and Expansion: Area Under the Concentration-Time Curve (AUC) of Lomvastomig
Timepoint [1] 0 0
Days 1, 2, 3, 5, 8, and 12 of Cycle 1; Days 1, 2, and 5 of Cycle 2; Day 1 of Cycles 3-4, Days 1, 2, 5, and 8 of Cycle 5 and Day 1 of Cycle 6 onwards (1 cycle is 14 days) through study completion (up to 27 months)
Secondary outcome [2] 0 0
Dose Escalation and Expansion: Maximum Concentration (Cmax) of Lomvastomig
Timepoint [2] 0 0
Days 1, 2, 3, 5, 8, and 12 of Cycle 1; Days 1, 2, and 5 of Cycle 2; Day 1 of Cycles 3-4, Days 1, 2, 5, and 8 of Cycle 5 and Day 1 of Cycle 6 onwards (1 cycle is 14 days) through study completion (up to 27 months)
Secondary outcome [3] 0 0
Dose Escalation and Expansion: Total Cnlearance (CL) of Lomvastomig
Timepoint [3] 0 0
Days 1, 2, 3, 5, 8, and 12 of Cycle 1; Days 1, 2, and 5 of Cycle 2; Day 1 of Cycles 3-4, Days 1, 2, 5, and 8 of Cycle 5 and Day 1 of Cycle 6 onwards (1 cycle is 14 days) through study completion (up to 27 months)
Secondary outcome [4] 0 0
Dose Escalation and Expansion: Volume of Distribution at Steady State of Lomvastomig
Timepoint [4] 0 0
Days 1, 2, 3, 5, 8, and 12 of Cycle 1; Days 1, 2, and 5 of Cycle 2; Day 1 of Cycles 3-4, Days 1, 2, 5, and 8 of Cycle 5 and Day 1 of Cycle 6 onwards (1 cycle is 14 days) through study completion (up to 27 months)
Secondary outcome [5] 0 0
Dose Escalation and Expansion: Terminal Half-Life (t1/2) of Lomvastomig
Timepoint [5] 0 0
Days 1, 2, 3, 5, 8, and 12 of Cycle 1; Days 1, 2, and 5 of Cycle 2; Day 1 of Cycles 3-4, Days 1, 2, 5, and 8 of Cycle 5 and Day 1 of Cycle 6 onwards (1 cycle is 14 days) through study completion (up to 27 months)
Secondary outcome [6] 0 0
Dose Escalation and Expansion: Number of Participants with Anti-Drug Antibodies
Timepoint [6] 0 0
Day 1 of Cycles 1 to 5; Day 1 of Cycle 7, and every 6 cycles (1 cycle is 14 days) afterwards through study completion (up to 27 months)
Secondary outcome [7] 0 0
Expansion: Number of Participants with at Least One Adverse Event, Severity Graded According to NCI CTCAE v5.0
Timepoint [7] 0 0
Up to 27 months
Secondary outcome [8] 0 0
Expansion: Examine Profile and Status of T-cell Proliferation/Activation in Tumor Biopsies and Peripheral Blood
Timepoint [8] 0 0
Days 1, 2, and 8 of Cycles 1 and 5; Day 1 of Cycles 2 and 3; and Day 1 of Cycles 9, 22, 35, and 48 (1 cycle is 14 days) through study completion (up to 27 months)
Secondary outcome [9] 0 0
Dose Escalation: Receptor Occupancy of Lomvastomig, Assessed via an Ex-Vivo Assay
Timepoint [9] 0 0
Days 1 and 8 of Cycles 1 and 5; Day 1 of Cycles 2 and 3; and Day 1 of Cycles 9, 22, 35, and 48 (1 cycle is 14 days), and at study completion (up to 27 months)
Secondary outcome [10] 0 0
Dose Escalation: Objective Response Rate, Assessed According to RECIST v1.1
Timepoint [10] 0 0
Up to 27 months
Secondary outcome [11] 0 0
Dose Escalation: Disease Control Rate, Assessed According to RECIST v1.1
Timepoint [11] 0 0
Up to 27 months
Secondary outcome [12] 0 0
Dose Escalation: Duration of Response, Assessed According to RECIST v1.1
Timepoint [12] 0 0
Up to 27 months
Secondary outcome [13] 0 0
Dose Escalation: Progression Free Survival, Assessed According to RECIST v1.1
Timepoint [13] 0 0
Up to 27 months

Eligibility
Key inclusion criteria
General

* Part A: Patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient
* Eastern Cooperative Oncology Group Performance Status 0-1
* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
* Fresh biopsies may be required
* Negative HIV, hepatitis B, or hepatitis C test result
* Women of childbearing potential and male participants must agree to remain abstinent or use contraceptive methods as defined by the protocol

Additional Specific Inclusion Criteria for Participants with Melanoma:

* Histologically confirmed, unresectable stage III or stage IV melanoma
* Previously treated with approved anti-programmed death-ligand 1 (PD-L1)/anti-programmed death-1 (PD-1) agents with or without approved anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy and up to one additional treatment regimen

Additional Specific Inclusion Criteria for Participants with Non-small Cell Lung Cancer (NSCLC) who Previously Received Treatment for Metastatic Disease:

* Histologically confirmed advanced NSCLC
* Previously treated with approved PD-L1/PD-1 inhibitors and platinum-based chemotherapy
* Not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling to the study
* Participants must have experienced initial clinical benefit (stable disease or better) from most recent checkpoint inhibitor (CPI) therapy
* Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening

Additional Specific Inclusion Criteria for Participants with Non-small Cell Lung Cancer (NSCLC) who Previously Did Not Receive Treatment for Metastatic Disease:

* Histologically confirmed advanced NSCLC
* Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening

Additional Specific Inclusion Criteria for Participants with Small Cell Lung Cancer (SCLC):

* Histologically confirmed SCLC
* Participants may have had prior chemotherapy, radiation therapy, or declined approved therapies for SCLC

Additional Specific Inclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma (ESCC):

* Participants whose major lesion was histologically confirmed as squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus
* Patients who have previously received not more than 1 prior line of treatment for metastatic disease prior to enrolling to the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
General

* Pregnancy, lactation, or breastfeeding
* Known hypersensitivity to any of the components of RO7121661
* Active or untreated central nervous system (CNS) metastases
* An active second malignancy
* Evidence of concomitant diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
* Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection
* Treatment with oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
* Active or history of autoimmune disease or immune deficiency
* Prior treatment with adoptive cell therapies, such as CAR-T therapies
* Concurrent therapy with any other investigational drug <28 days or 5 half-lives of the drug, whichever is shorter, prior to the first RO7247669 administration
* Regular immunosuppressive therapy
* Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy
* Prior treatment with a T-cell immunoglobulin and mucin domain-3 (TIM-3) inhibitor

Additional Specific Exclusion Criteria for Participants with NSCLC who Previously Received Treatment for Metastatic Disease:

- Patients with the following mutations, rearrangements, translocations are not eligible: epidermal growth factor receptor (EGFR); anaplastic lymphoma kinase (ALK); ROS proto-oncogene 1 (ROS1), BRAFV600E, and neurotrophic receptor tyrosine kinase (NTRK)

Additional Specific Exclusion Criteria for Participants with NSCLC who Did Not Previously Receive Treatment for Metastatic Disease:

* Prior therapy for metastatic disease
* Adjuvant anti-PD-1 or anti-PD-L1 therapy

Additional Specific Exclusion Criteria for Participants with Small-Cell Lung Cancer (SCLC):

- Prior therapy with any immune CPIs (such as anti-PD-L1/PD-1, CTLA-4)

Additional Specific Exclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma (ESCC):

- Prior therapy with any immunomodulatory agents

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/10/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/07/2024
Sample size
Target
Accrual to date
Final
134
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
Denmark
State/province [3] 0 0
Herlev
Country [4] 0 0
Denmark
State/province [4] 0 0
København Ø
Country [5] 0 0
France
State/province [5] 0 0
Bordeaux
Country [6] 0 0
France
State/province [6] 0 0
Lyon
Country [7] 0 0
France
State/province [7] 0 0
Marseille
Country [8] 0 0
France
State/province [8] 0 0
St Herblain
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Seoul
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
Spain
State/province [11] 0 0
Navarra
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid
Country [14] 0 0
Spain
State/province [14] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03708328