Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of Selicrelumab (RO7009789) With Vanucizumab or Bevacizumab in Participants With Metastatic Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02665416
• Date of registration: 15/01/2016
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of Selicrelumab (RO7009789) With Vanucizumab or Bevacizumab in Participants With Metastatic Solid Tumors
• Scientific title: An Open-Label, Multicenter, Dose Escalation Phase Ib Study With Expansion Cohorts to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Therapeutic Activity of RO7009789 (CD40 Agonistic Monoclonal Antibody) in Combination With Vanucizumab (Anti-Ang2 and Anti-VEGF Bi-Specific Monoclonal Antibody, Part I) or Bevacizumab (Anti-VEGF Monoclonal Antibody, Part II) in Patients With Metastatic Solid Tumors
• Date of first enrolment: January 25, 2016
• Target sample size: 94
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02665416
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Belgium, Canada, Denmark, France, Italy, Netherlands, Spain, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Part I: Histologically confirmed advanced/metastatic solid tumor (except prostate
cancer and squamous non-small cell lung cancer [NSCLC])

- Part II: Histologically confirmed advanced/metastatic platinum-resistant ovarian
carcinoma (aPROC), head and neck squamous cell carcinoma (HNSCC), or non-squamous
NSCLC previously treated with anti-PD-L1/PD-1 inhibitor alone or in combination (e.g.
atezolizumab, nivolumab, pembrolizumab, durvalumab, avelumab)

- Checkpoint inhibitor (CPI)- experienced patients must have experienced documented
disease progression on or after PD-L1/PD-1 inhibitor therapy

- In CPI-experienced patients, the PD-L1/PD-1 inhibitor must have been part of the most
recent systemic anticancer therapy administered prior to study enrollment

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Life expectancy >/= 16 weeks

- Adequate hematologic, renal, hepatic, and cardiovascular function

- Measurable disease per Response Evaluation Criteria in Solid Tumors, v 1.1 (RECIST
v1.1)

- Tumors must be acceptable for biopsy. Participants in Part II may be enrolled without
a biopsy if the collection is not clinically feasible.

- Agreement to use adequate contraceptive measures among men or among women of
childbearing potential

Exclusion Criteria:

- Prostate cancer or squamous NSCLC

- Recent systemic anti-cancer treatment

- Prior treatment with anti-programmed death (PD) 1 or anti-programmed death ligand
(PD-L) 1 therapeutic antibody, vanucizumab, or compounds targeting cluster of
differentiation (CD) 40 less than 4 weeks or 5xt1/2 (whichever is shorter) prior to
enrollment

- Part II: Treatment targeting vascular endothelial growth factor (VEGF) or receptor
within 12 months prior to enrollment

- Systemic immunosuppressive medication within 2 weeks prior to day 1 of cycle 1

- Chronic daily treatment with non-steroidal anti-inflammatory drugs

- Unacceptable/unresolved toxicity from prior anti-cancer therapy

- Patients who have had a surgical procedure or significant traumatic injury within 28
days prior to initiation of study treatment, or a core biopsy or other minor surgical
procedure within 7 days prior to initiation of study treatment

- Bisphosphonate therapy for symptomatic hypercalcemia

- Significant vascular disease

- History of hypertensive crisis or hypertensive encephalopathy

- Current or recent use of aspirin (>325 mg/day) or clopidogrel (>75 mg/day)

- History of vein thrombosis/thromboembolism, or use of anticoagulants within 7 days
prior to study drug

- Primary tumor in place in participants with colorectal cancer, or evidence of bowel
involvement (metastasis, direct tumor invasion) in participants with other
non-gastrointestinal cancer

- Significant cardiovascular or cerebrovascular disease within 6 months prior to D1 of
C1

- History of fistula, bowel obstruction, perforation, or abscess

- Prior radiotherapy to pelvis or abdomen, recto-sigmoid involvement, or bowel
involvement among participants with aPROC

- Severe non-healing wound, active ulcer or untreated bone fracture

- Pregnant or lactating women

- History of autoimmune disease

- Human immunodeficiency virus (HIV) or hepatitis B or C

- Severe infection or receipt of a live/attenuated vaccine within 4 weeks prior to D1 of
C1

- Other significant malignancies within 3 years prior to D1 of C1

- Allergy/hypersensitivity to study drug

- Prior allogeneic bone marrow or solid organ transplant

- Other conditions/findings that may contraindicate use of study drug

- Major surgery within 4 weeks prior to study drug

- Known clinically significant liver disease

- History of hemoptysis or bleeding diathesis, or known coagulopathies

- Known symptomatic or untreated central nervous system (CNS) malignancy



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Advanced/Metastatic Solid Tumors

Intervention(s)

Drug: Selicrelumab

Drug: Vanucizumab

Drug: Bevacizumab

Primary Outcome(s)

Part II: Percentage of Participants With Best Overall Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Percentage of Participants With Adverse Events (AEs) [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

MTD of Selicrelumab in Combination With Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part II: Percentage of Participants With Disease Control per RECIST v1.1 Criteria [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part II: Clinical Activity of SC Selicrelumab in Combination with Bevacizumab as Assessed by Response Evaluation in Solid Tumors, Version 1.1 (RECIST v1.1) [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part II: Progression-free Survival (PFS) per RECIST v1.1 Criteria [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part II: Duration of Objective Response per RECIST v1.1 Criteria [Time Frame: TBaseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Recommended Phase II Dose of Selicrelumab in Combination With Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Secondary Outcome(s)

Area Under the Concentration-Time Curve From Time 0 to Last Measureable Concentration (AUClast) of Selicrelumab Following Subcutaneous (SC) Administration [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Change in Peripheral Blood Level of Cytokines [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Percentage of Participants With Best overall Response Immune-Related Response Criteria (irRC) [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Clinical Activity of SC Selicrelumab in Combination with Bevacizumab as Assessed by Unidimensional Immune-Related Response Criteria (irRC) [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Concentration at the end of Infusion (Cend) of Bevacizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: t1/2 of Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Overall Survival (OS) [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first (up to approximately 42 months)]

Part I: Percentage of Participants With Disease Control per RECIST v1.1 Criteria [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Maximum Concentration (Cmax) of Selicrelumab Following SC Administration [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Minimum Concentration (Cmin) of Bevacizumab after Infusion [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: Progression-free Survival (PFS) per RECIST v1.1 Criteria [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Apparent Terminal Half-Life (t1/2) of Selicrelumab Following SC Administration [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Selicrelumab Following SC Administration [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Time to Maximum Concentration (Tmax) of Selicrelumab Following SC Administration [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Change in Blood and Tumor Tissue Immune Cell Subpopulations [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Duration of Objective Response per irRC [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: CL of Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Apparent Volume of Distribution (Vd/F) of Selicrelumab Following SC Administration [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Change in Blood Soluble Proteins [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: Clinical Activity of SC Selicrelumab in Combination with Bevacizumab as Assessed by Response Evaluation in Solid Tumors, Version 1.1 (RECIST v1.1) [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: AUCinf of Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: AUClast of Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: Concentration at the End of Infusion (Cend) of Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Percentage of Participants With Anti-Drug Antibodies (ADAs) to Selicrelumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: Percentage of Participants With Best Overall Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Percentage of Participants With Disease Control per irRC [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Apparent Clearance (CL/F) of Selicrelumab Following SC Administration [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: Duration of Objective Response per RECIST v1.1 Criteria [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Part I: Vss of Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Percentage of Participants with ADAs to Vanucizumab [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

PFS per irRC [Time Frame: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)]

Secondary ID(s)

RG7876

2015-003480-11

BP29889

Source(s) of Monetary Support

Please refer to primary and secondary sponsors