Advanced/Metastatic Solid TumorsPhase 1NCT02665416
Study Evaluating the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Therapeutic Activity of Selicrelumab (RO7009789) With Vanucizumab or Bevacizumab in Participants With Metastatic Solid Tumors
A Phase 1 study testing Selicrelumab, Vanucizumab and Bevacizumab in people with Advanced/Metastatic Solid Tumors, run by Hoffmann-La Roche at 16 sites in 7 countries.
Trial summary
This open-label, two-part study is designed to assess the safety, PK, PD, and therapeutic activity of Selicrelumab in combination with vanucizumab or bevacizumab in participants with metastatic solid tumors not amenable to standard treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced/Metastatic Solid Tumors
- What is being tested?
- Selicrelumab, Vanucizumab and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 16 sitesin 7 countries
- Study dates
- 25 Jan 2016to 30 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
16 sites in 7 countries.
16 sites in 7 countries
United States5 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Univ of CO Health Science Ctr
Denver, Colorado, 80262
Cedars Sinai Medical Center
Los Angeles, California, 90048
Yale Cancer Center; Medical Oncology
New Haven, Connecticut, 06520
Spain5 sites
Hospital del Mar; Servicio de Oncologia
Barcelona, 08003
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, 08035
ICO L'Hospitalet; Servicio de oncologia medica
L'Hospitalet de Llobregat, Barcelona, 08908
START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
Madrid, 28050
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Valencia, 46010
Netherlands2 sites
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, 1066 CX
Erasmus Medisch Centrum
Rotterdam, 3015 GD
Canada1 site
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, M5G 2M9
About this study
Official 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
This open-label, two-part study is designed to assess the safety, PK, PD, and therapeutic activity of Selicrelumab in combination with vanucizumab or bevacizumab in participants with metastatic solid tumors not amenable to standard treatment. Part I (dose escalation) is designed to establish the maximum tolerated dose (MTD) of Selicrelumab in this combination. Part II (expansion) is intended to characterize the safety and tolerability of Selicrelumab in combination with bevacizumab among indication-specific cohorts and to confirm the recommended dose.
- Conditions
- Advanced/Metastatic Solid Tumors
- Being tested
- Selicrelumab, Vanucizumab, Bevacizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelicrelumabDrug
Also called RO7009789
Selicrelumab will be provided as concentrate for solution to be administered via SC injection
VanucizumabDrug
Vanucizumab will be provided as solution to be administered via IV infusion.
BevacizumabDrug
Bevacizumab will be administered via IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Part I: Selicrelumab, Vanucizumab/Bevacizumab | Experimental | Participants will receive a fixed dose of vanucizumab, 2 grams via IV infusion on Days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC in ascending dose levels on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part I of the study (expected 24 months). Due to the discontinuation of Vanucizumab development, Participants ongoing in Part I will switch from Vanucizumab to Bevacizumab. All the dose escalation has been performed using Vanucizumab. Receives: Drug: Selicrelumab; Drug: Vanucizumab |
| Part II: Selicrelumab, Bevacizumab | Experimental | Bevacizumab will be administered via IV infusion on days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC after the Bevacizumab infusion at the dose determined in the Part I of the study on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part II of the study (expected 18 months). Receives: Drug: Selicrelumab; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
From Day (D) 1 until D28 of Cycle (C)1 (cycle length=28 days)
Measured: 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
From D1 until D28 of C1 (cycle length=28 days)
Measured: Baseline 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
From D1 until D28 of C1 (cycle length=28 days)
Measured: 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)
From D1 of C1 until treatment discontinuation and approximately 45 days after last dose (cycle length=28 days)
Measured: 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)
From D1 of C1 through safety follow up visit (45 days post final dose; Cycle = 28 days)
Measured: 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 Best Overall Response per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: TBaseline 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)
Secondary outcomes (31)
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Selicrelumab
Predose (-1 hour [h]) on D2 of C1, C2, C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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
Predose (within 10 minutes [min] before infusion) on D1 of C1, C2, C4, and every 2 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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 Last Measureable Concentration (AUClast) of Selicrelumab Following Subcutaneous (SC) Administration
Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (up to 24 months in Part I and 18 months in Part II; cycle length=28 days)
Measured: 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
Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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
Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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
Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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
Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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
Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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
Predose (-1 h) and 3 (only C2), 4, 8, 24, 48, 72 h postdose on C1 and C2; predose (-1 h) and 8 h postdose on C3, C4, C7, and every 3 cycles until/at disease progression and/or 45 days after last dose (cycle length=28 days)
Measured: 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
Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days)
Measured: 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
Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days)
Measured: 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
Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days)
Measured: 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
Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days)
Measured: 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
Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days)
Measured: 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
Predose (within 10 min) on D1 of C1, C2, C4, C6, C8, every 2 cycles thereafter disease progression and/or 45 days after last dose; predose (within 10 min), end of infusion (infusion duration=60-90 min) on D15 of C1 to C9 and each cycle thereafter until disease progression and/or 45 days after last dose; 6 and 24 h postdose on D15 of C1 and C8 (cycle length = 28 days)
Measured: 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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 Disease Control per RECIST v1.1 Criteria
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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)
From D1 of C1 through safety follow up visit (45 days post final dose; cycle length = 28 days)
Measured: 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
Part I: C1 at D1 pre-dose Vanicizumab, D4, D9 (D15 pre and 6h post for cohorts 8 onwards); C2 at D1 and D9; C4,7,10 at D1 and D9; PD Part II: C1 D1(pre), D3,D8,D15; C2,4,7,10 D1,D8; PD
Measured: 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
C1D1 pre-dose Vanicizumab, C1 D2 pre-dose Selicrelumab and 3h post-dose Selicrelumab, C2D1 pre-dose Vanicizumab, C2D2 pre-dose Selicrelumab and 3h post-dose Selicrelumab, C4 D2 pre-dose Selicrelumab and 3h post-dose, PD
Measured: 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
D1, 2, 3, 9, 15 of C1; D1, 3, 9, 15 of C2; D1 of C 4,5; D1, 15 of C7, D1 of C10, PD
Measured: 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)
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)
PFS per irRC
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
Measured: 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)
From D1 of C1 through safety follow up visit (45 days post final dose; cycle length = 28 days)
Measured: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)
Overall Survival (OS)
Measured: Baseline until Participant's discontinuation or death, whichever occurs first (up to approximately 42 months)
Concentration at the end of Infusion (Cend) of Bevacizumab
D1 and D15 of C1, then D1 of every cycle until C7; at radiographical disease progression/tumor regression; at safety follow up visit (45 days post final dose; Cycle = 28 days)
Measured: 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
D1 and D15 of C1, then D1 of every cycle until C7; at radiographical disease progression/tumor regression; at safety follow up visit (45 days post final dose; Cycle = 28 days)
Measured: Baseline until Participant's discontinuation or death, whichever occurs first, as per schedule in the description (up to approximately 42 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2016 (estimated)
- Study start25 Jan 2016
- Primary completion30 Oct 2019
- Study completion30 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced/Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02665416
- Sponsor's protocol ID
- BP29889
- Other IDs
- 2015-003480-11, RG7876, 2015
- Status last verified
- Apr 2020
- First submitted
- 15 Jan 2016
- Last updated
- 7 Apr 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02665416
- Acronym / sponsor ID
- BP29889
- Conditions
- Advanced/Metastatic Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 25 Jan 2016 (actual)
- Primary completion
- 30 Oct 2019 (actual)
- Study completion
- 30 Oct 2019 (actual)
- First posted
- 27 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label, two-part study is designed to assess the safety, PK, PD, and therapeutic activity of Selicrelumab in combination with vanucizumab or bevacizumab in participants with metastatic solid tumors not amenable to standard treatment. Part I (dose escalation) is designed to establish the maximum tolerated dose (MTD) of Selicrelumab in this combination. Part II (expansion) is intended to characterize the safety and tolerability of Selicrelumab in combination with bevacizumab among indication-specific cohorts and to confirm the recommended dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part I: Selicrelumab, Vanucizumab/Bevacizumab | Experimental | Drug: Selicrelumab, Drug: VanucizumabParticipants will receive a fixed dose of vanucizumab, 2 grams via IV infusion on Days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC in ascending dose levels on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part I of the study (expected 24 months). Due to the discontinuation of Vanucizumab development, Participants ongoing in Part I will switch from Vanucizumab to Bevacizumab. All the dose escalation has been performed using Vanucizumab. |
| Part II: Selicrelumab, Bevacizumab | Experimental | Drug: Selicrelumab, Drug: BevacizumabBevacizumab will be administered via IV infusion on days 1 and 15 of every 28-day cycle. Selicrelumab will be given SC after the Bevacizumab infusion at the dose determined in the Part I of the study on Day 2 of Cycles 1 to 4 and every third cycle thereafter. Treatment will continue as long as the participant experiences clinical benefit or until unacceptable toxicity, withdrawal of consent, or the end of Part II of the study (expected 18 months). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (30 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelicrelumabAlso: RO7009789Selicrelumab will be provided as concentrate for solution to be administered via SC injection | Drug | Part I: Selicrelumab, Vanucizumab/Bevacizumab, Part II: Selicrelumab, Bevacizumab |
| VanucizumabVanucizumab will be provided as solution to be administered via IV infusion. | Drug | Part I: Selicrelumab, Vanucizumab/Bevacizumab |
| BevacizumabBevacizumab will be administered via IV infusion. | Drug | Part II: Selicrelumab, Bevacizumab |
Primary outcome
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)
From Day (D) 1 until D28 of Cycle (C)1 (cycle length=28 days)
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)
From D1 until D28 of C1 (cycle length=28 days)
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)
From D1 until D28 of C1 (cycle length=28 days)
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)
From D1 of C1 until treatment discontinuation and approximately 45 days after last dose (cycle length=28 days)
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)
From D1 of C1 through safety follow up visit (45 days post final dose; Cycle = 28 days)
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)
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
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)
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
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)
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
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)
Tumor assessments at Screening and on D1 of C3, C5, C7; and every 12 weeks thereafter until disease progression (cycle length=28 days)
31 secondary outcomes
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)
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)
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)
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)
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)
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)
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)
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)
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)
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: 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: 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)
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)
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)
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)
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)
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: 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 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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Overall Survival (OS)
Time frame: Baseline until Participant's discontinuation or death, whichever occurs first (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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
16 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selicrelumab, Vanucizumab and Bevacizumab in people with Advanced/Metastatic Solid Tumors, run by Hoffmann-La Roche at 16 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Spain, Netherlands, Belgium, Canada and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2020.