A Study of Selicrelumab (RO7009789) in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Solid Tumors

NCT02304393 | Completed Phase 1

• 2 other identifiers: BP293922014-002835-32
• Study Type: interventional
• Target: 140
• Locations: 6 countries
• Sites: 11

Brief Summary

This is an open-label, multicenter study designed to assess the safety, pharmacokinetics, pharmacodynamics and activity of Selicrelumab administered in combination with Atezolizumab (ATZ) in participants with metastatic or locally advanced solid tumors. The study will be conducted in two Parts (I and II), with Part I divided into Parts IA and IB. All participants will be followed up for survival until death or loss of follow-up after the last visit or withdrawal of consent.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (15)

• Part IA: Percentage of Participants with Adverse Events and Serious Adverse Events

  Baseline up to 28 Days After the Last Dose (Approximately 38 Months)

• Part IB: Percentage of Participants with Adverse Events and Serious Adverse Events

  Baseline up to 28 Days After the Last Dose (Approximately 38 Months)

• Part IB: Percentage of Participants With Dose-Limiting Toxicities (DLTs)

  Cycle 1 Day 1 up to Cycle 2 Day 2 (Cycle length = 21 days)

• Part IB: Maximum Tolerated Dose (MTD) of Selicrelumab

  Cycle 1 Day 1 up to Cycle 2 Day 2 (Cycle length = 21 days)

• Part IB: Recommended Part II Dose of Selicrelumab

  Cycle 1 Day 1 up to Cycle 2 Day 2 (Cycle length = 21 days)

• Part II: Percentage of Participants with Adverse Events and Serious Adverse Events

  Baseline up to 28 days after the last dose (approximately 38 months)

• Part II: Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: Progression-Free Survival (PFS), as Determined by Investigator Using RECIST Version 1.1

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: Duration of Objective Response, as Determined by Investigator Using RECIST Version 1.1

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: Percentage of Participants With Disease Control, as Determined by Investigator Using RECIST Version 1.1

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: Percentage of Participants With Disease Control, as Determined by Investigator Using Unidimensional irRC

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: PFS, as Determined by Investigator Using Unidimensional irRC

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: Percentage of Participants With Best Overall Response, as Determined by Investigator Using Unidimensional Immune-Related Response Criteria (irRC)

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: Duration of Objective Response, as Determined by Investigator Using Unidimensional irRC

  Baseline up to PD or death due to any cause, whichever occurs first (up to approximately 38 months)

• Part II: Overall Survival

  Baseline up to death due to any cause (up to approximately 38 months)

Secondary Outcomes (58)

• Part IA: Area Under the Concentration Time Curve (AUC) of Selicrelumab

  Pre Selicrelumab dose (1hour[Hr]) on Cycle(Cy)1 Day1(D1); 4,8,24,48,72Hr post D1dose; D8,15 of Cy1; D1 Cy2&3 (10 minutes pre ATZ dose); at radiographic disease progression (PD)(up to 38 months);28&150 days after last ATZ dose (up to38months)(Cy=21days)

• Part IA: Maximum Serum Concentration (Cmax) of Selicrelumab

  Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 minutes [min] pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)

• Part IA: Time to Cmax (Tmax) of Selicrelumab

  Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)

• Part IA: Minimum Serum Concentration Under Steady-State (Cmin) of Selicrelumab

  Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)

• Part IA: Apparent Clearance (CL/F) of Selicrelumab

  Pre Selicrelumab dose (within 1 Hr) on Cy1 D1; 4, 8, 24, 48,72Hr post D1dose; D8, D15 of Cy1; D1 of Cy2 & 3 (10 min pre ATZ dose); at radiographic PD (up to 38 months); 28 & 150 days after last ATZ dose (up to 38 months) (Cy=21days)

Study Arms (4)

Part IA: Selicrelumab (IV) + Atezolizumab

EXPERIMENTAL

Selicrelumab at a dose of 16 milligrams (mg) will be administered intravenously (IV) on Day 1 of Cycle 1 (first cycle in this group was of 42 days, and subsequent 21-day cycles); and atezolizumab 1200 mg will be administered IV after 6 weeks on Day 1 of Cycle 2, followed by every 3 weeks during Part IA until disease progression, death, loss of follow-up, or withdrawal of consent.

Drug: Atezolizumab; Drug: Selicrelumab

Part IA: Selicrelumab(SC) + Atezolizumab

EXPERIMENTAL

Selicrelumab at a starting dose of 1 mg will be administered subcutaneously (SC) on Day 1 of Cycle 1 (21-day cycle) which will follow escalation in sequential cohorts; and atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 2, and followed by every 3 weeks during Part IA as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity.

Drug: Atezolizumab; Drug: Selicrelumab

Part IB: Selicrelumab + Atezolizumab

EXPERIMENTAL

Selicrelumab will be administered at a starting dose of 1 mg SC on Day 2 of Cycle 1 (21-day cycle) which will follow escalation in sequential cohorts; and atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 1, and followed by every 3 weeks during Part IB as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity.

Drug: Atezolizumab; Drug: Selicrelumab

Part II: Selicrelumab + Atezolizumab

EXPERIMENTAL

Atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 1, and followed by every 3 weeks; and Selicrelumab will be administered at the dose defined in Part IB (not exceeding 80 mg SC \[unless IV administration in Part IB demonstrates better benefit/risk ratio\]) on Day 2 (1 day after atezolizumab administration) of every second cycle from Cycles 1 to 7, and every fourth cycle thereafter during Part II as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity.

Drug: Atezolizumab; Drug: Selicrelumab

Interventions

Atezolizumab DRUG

Atezolizumab will be administered as per the dosage regimen mentioned in respective arm descriptions.

Also known as: MPDL3280A, Tecentriq

Part IA: Selicrelumab (IV) + Atezolizumab; Part IA: Selicrelumab(SC) + Atezolizumab; Part IB: Selicrelumab + Atezolizumab; Part II: Selicrelumab + Atezolizumab

Selicrelumab DRUG

Selicrelumab will be administered as per the dosage regimen mentioned in respective arm descriptions.

Also known as: RO7009789

Part IA: Selicrelumab (IV) + Atezolizumab; Part IA: Selicrelumab(SC) + Atezolizumab; Part IB: Selicrelumab + Atezolizumab; Part II: Selicrelumab + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors, which are not amenable to standard therapy
• Part I: histologically confirmed diagnosis of advanced/metastatic small and large bowel carcinomas (small bowel and CRC), CPI-experienced non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC)
• Part II: CPI-experienced NSCLC patients must have experienced documented disease progression on or after PD-L1 or PD-1 inhibitor therapy (investigational or approved): screening tumor assessment should confirm prior progression
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than or equal to (\>/=) 16 weeks
• Adequate hematologic and end organ function
• Measurable disease per RECIST Version 1.1
• Ability to comply with the protocol requirements
• Female participants of childbearing potential must have a negative pregnancy test (urine/serum) within seven days prior to the first study drug administration
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than (\<) 1% per year during the treatment period and for at least 5 months after the last dose of study treatment
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 28 days after the last dose of study treatment

You may not qualify if:

• If one of the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1 Day 1) are: soluble interleukin 2 receptor (sCD25) greater than (\>) 2 × upper limit of normal (ULN); Serum ferritin \>1000 nanograms per milliliter (ng/mL)
• Any approved anti-cancer therapy that includes chemotherapy, hormonal therapy, or radiotherapy within 2 weeks prior to the first dose of study treatment; the following is, however, allowed: Palliative radiotherapy for bone metastases less than or equal to (\</=) 2 weeks prior to Cycle 1 Day 1
• Adverse events from prior anti-cancer therapy that have not resolved to Grade \</= 1 except for any grade alopecia and \</= Grade 2 peripheral neuropathy
• Bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (example: bone metastasis or osteoporosis) is allowed
• Uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent drainage procedures (one monthly or more frequently). Participants with indwelling catheters are allowed
• Known clinically significant liver disease which includes active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
• History (within the previous year) of congestive heart failure, stroke, arrhythmia, or myocardial infarction
• History of peripheral venous thrombosis or thromboembolic event (within 12 months prior to Cycle 1 Day 1)
• Significant cardio- or cerebrovascular disease within 6 months prior to Cycle 1 Day 1
• Known hereditary or acquired coagulopathies
• Clinically meaningful proteinuria
• Requiring dialysis (peritoneal or hemodialysis)
• Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS metastases: participants with asymptomatic-treated CNS metastases may be enrolled after consultation with the Medical Monitor, provided they meet the following criteria:
• Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
• No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1 Day 1

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (11)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital / McGill University

Montreal, Quebec, H3T 1E2, Canada

Location

Rigshospitalet; Onkologisk Klinik

København Ø, 2100, Denmark

Location

Aphm; Cpcet

Marseille, 13385, France

Location

Hopital Saint Louis, Service D Oncologie Medicale

Paris, 75475, France

Location

Institut Gustave Roussy; Sitep

Villejuif, 94805, France

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Erasmus Medisch Centrum Rotterdam; Lokatie Daniel den Hoed

Rotterdam, 3015 GD, Netherlands

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

START Madrid. Centro Integral Oncologico Clara Campal; CIOCC

Madrid, 28050, Spain

Location

MeSH Terms

Interventions

atezolizumab; selicrelumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2014
• First Posted: December 1, 2014
• Study Start: December 12, 2014
• Primary Completion: November 7, 2019
• Study Completion: November 7, 2019
• Last Updated: December 13, 2019

Record last verified: 2019-12

Locations

CA (2); FR (3); US (1); NL (2); ES (2); DK (1)