Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03708328
Previous Study | Return to List | Next Study

A Dose Escalation and Expansion Study of RO7121661, a PD-1/TIM-3 Bispecific Antibody, in Participants With Advanced and/or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03708328
Recruitment Status : Recruiting
First Posted : October 17, 2018
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:

This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD) study of single agent RO7121661, an anti PD-1 (programmed death-1) and TIM-3 (T-cell immunoglobulin and mucin domain 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. The study consists of 2 parts: Dose Escalation (Part A) and Expansion (Parts B1, B2, B3, B4, and B5). The Dose Escalation part will be conducted first to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) based on safety, tolerability, pharmacokinetic, and/or the pharmacodynamic profile of escalating doses of RO7121661. The Expansion part will enroll tumor-specific cohorts to evaluate anti-tumor activity of the MTD and/or RDE of RO7121661 from Part A (Q2W) and to confirm safety and tolerability in participants with selected tumor types.

Recruitment into the Expansion Part B4: SCLC Cohort is now closed.


Condition or disease Intervention/treatment Phase
Solid Tumors Metastatic Melanoma Non-small Cell Lung Cancer (NSCLC) Small Cell Lung Cancer (SCLC) Esophageal Squamous Cell Carcinoma (ESCC) Drug: RO7121661 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 15, 2018
Estimated Primary Completion Date : May 31, 2023
Estimated Study Completion Date : May 31, 2023


Arm Intervention/treatment
Experimental: Dose Escalation Part A: Once Every 2 Weeks (Q2W)
RO7121661 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.
Drug: RO7121661
RO7121661 will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.
Other Name: RG7769

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 RO7121661 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.
Drug: RO7121661
RO7121661 will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.
Other Name: RG7769

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 RO7121661 for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.
Drug: RO7121661
RO7121661 will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.
Other Name: RG7769

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 RO7121661 for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.
Drug: RO7121661
RO7121661 will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.
Other Name: RG7769

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 RO7121661 for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.
Drug: RO7121661
RO7121661 will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.
Other Name: RG7769

Experimental: Expansion Part B5: ESCC Cohort
This cohort will comprise participants with CPI-naïve esophageal squamous cell carcinoma (ESCC). The starting dose of RO7121661 for Expansion will be derived from the MTD/RDE and the best dosing schedule determined during Dose Escalation.
Drug: RO7121661
RO7121661 will be administered intravenously (IV) with a flat dose on the schedule described for each study arm.
Other Name: RG7769




Primary Outcome Measures :
  1. Dose Escalation: Number of Participants with a Dose-Limiting Toxicity (DLT) [ Time Frame: For Part A (1 cycle is 14 days): From Cycle 1 Day 1 to Cycle 2 Day 7 (up to 35 days) ]
  2. 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) [ Time Frame: Up to 27 months ]
  3. Expansion: Objective Response Rate, Assessed According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Up to 27 months ]
  4. Expansion: Disease Control Rate, Assessed According to RECIST v1.1 [ Time Frame: Up to 27 months ]
  5. Expansion: Duration of Response, Assessed According to RECIST v1.1 [ Time Frame: Up to 27 months ]
  6. Expansion: Progression Free Survival, Assessed According to RECIST v1.1 [ Time Frame: Up to 27 months ]

Secondary Outcome Measures :
  1. Dose Escalation and Expansion: Area Under the Concentration-Time Curve (AUC) of RO7121661 [ Time Frame: 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) ]
  2. Dose Escalation and Expansion: Maximum Concentration (Cmax) of RO7121661 [ Time Frame: 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) ]
  3. Dose Escalation and Expansion: Total Clearance (CL) of RO7121661 [ Time Frame: 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) ]
  4. Dose Escalation and Expansion: Volume of Distribution at Steady State of RO7121661 [ Time Frame: 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) ]
  5. Dose Escalation and Expansion: Terminal Half-Life (t1/2) of RO7121661 [ Time Frame: 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) ]
  6. Dose Escalation and Expansion: Number of Participants with Anti-Drug Antibodies [ Time Frame: 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) ]
  7. Expansion: Number of Participants with at Least One Adverse Event, Severity Graded According to NCI CTCAE v5.0 [ Time Frame: Up to 27 months ]
  8. Expansion: Examine Profile and Status of T-cell Proliferation/Activation in Tumor Biopsies and Peripheral Blood [ Time Frame: 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) ]
  9. Dose Escalation: Receptor Occupancy of RO7121661, Assessed via an Ex-Vivo Assay [ Time Frame: 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) ]
  10. Dose Escalation: Objective Response Rate, Assessed According to RECIST v1.1 [ Time Frame: Up to 27 months ]
  11. Dose Escalation: Disease Control Rate, Assessed According to RECIST v1.1 [ Time Frame: Up to 27 months ]
  12. Dose Escalation: Duration of Response, Assessed According to RECIST v1.1 [ Time Frame: Up to 27 months ]
  13. Dose Escalation: Progression Free Survival, Assessed According to RECIST v1.1 [ Time Frame: Up to 27 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

General Inclusion Criteria:

  • 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

Exclusion Criteria:

General Exclusion Criteria:

  • 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03708328


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: NP40435 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
Show Show 20 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03708328    
Other Study ID Numbers: NP40435
2018-000982-35 ( EudraCT Number )
First Posted: October 17, 2018    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Qualified researchers may request access to individual patient level data through the 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 Sharing of Clinical Study 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).


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Small Cell Lung Carcinoma
Esophageal Squamous Cell Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms by Histologic Type
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases