NCT01354431

BMS-936558 (MDX-1106) In Subjects With Advanced/Metastatic Clear-Cell Renal Cell Carcinoma (RCC)

Completed Phase 2 Results posted Last updated 12 May 2022

What this trial tests

Phase 2 trial testing nivolumab in Renal Cell Carcinoma in 168 participants. Completed in 15 April 2021.

Timeline

31 May 2011

Primary endpoint
15 May 2013

15 April 2021

Quick facts

Lead sponsor	Bristol-Myers Squibb
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	168
Start date	31 May 2011
Primary completion	15 May 2013
Estimated completion	15 April 2021
Sites	41 locations across Finland, Italy, Canada, United States

Drugs / interventions tested

• nivolumab (nivolumab) — full drug profile →
• nivolumab (nivolumab) — full drug profile →
• nivolumab (nivolumab) — full drug profile →

Conditions studied

• Renal Cell Carcinoma — all drugs for Renal Cell Carcinoma →

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Renal Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · From randomization to disease progression or death (up to approximately 2 years)

PFS is defined as the time from randomization to date of first disease progression (either clinical or radiographic progression, as assessed by the investigator). Tumor assessments (radiographic scans) were done every 6 weeks from randomization for the first 12 months, then every 12 weeks until progression. Survival was assessed every 3 months. The analysis of PFS was conducted after approximately 116 events (progression or death), approximately 2 years. PFS was calculated based on investigator's assessment of first date of progression (either clinical or radiographic progression) or date of d

Group	Value	95% CI
Nivolumab 0.3 mg/kg	2.63	1.81 – 3.02
Nivolumab 2 mg/kg	4.11	2.86 – 5.39
Nivolumab 10 mg/kg	4.17	2.79 – 5.49

Best Overall Response Rate (BORR) Secondary · From randomization until disease progression or discontinuation of study therapy (up to approximately 2 years)

BORR is defined as the percentage of participants whose best response is either partial response (PR) or complete response (CR). Tumor response was evaluated by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. PR: at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. 80% confidence interval is based on the Clopper and Pearson method

Group	Value	95% CI
Nivolumab 0.3 mg/kg	20.0	13.4 – 28.2
Nivolumab 2 mg/kg	24.1	16.6 – 33.1
Nivolumab 10 mg/kg	20.4	13.4 – 29.1

Overall Survival (OS) Secondary · From randomization to to date of death (up to approximately 8 years)

OS is defined as the time from date of randomization until date of death. If the participant did not die, overall survival will be censored on the last date the participant was known to be alive. Survival status is collected at each visit during treatment and every 3 months during follow-up. OS is based on Kaplan-Meier estimates.

Group	Value	95% CI
Nivolumab 0.3 mg/kg	18.45	16.23 – 23.98
Nivolumab 2 mg/kg	25.46	19.78 – 31.24
Nivolumab 10 mg/kg	24.82	15.31 – 25.95

Number of Participants Experiencing Adverse Events Secondary · From first dose to 30 days following last dose (up to approximately 6 years)

Number of participants experiencing different types of events, including Adverse Events (AEs), Drug-related AEs, AEs leading to discontinuation, Drug-related AEs leading to discontinuation, Serious Adverse Events (SAEs), Drug-related SAEs. Events are classified based on the NCI Common Terminology Criteria (CTC) version 4.0

Any AEs

Group	Value	95% CI
Nivolumab 0.3 mg/kg	58
Nivolumab 2 mg/kg	54
Nivolumab 10 mg/kg	53

Drug-related AEs

Group	Value	95% CI
Nivolumab 0.3 mg/kg	44
Nivolumab 2 mg/kg	36
Nivolumab 10 mg/kg	41

AEs leading to discontinuation

Group	Value	95% CI
Nivolumab 0.3 mg/kg	6
Nivolumab 2 mg/kg	10
Nivolumab 10 mg/kg	10

Drug-related AEs leading to discontinuation

Group	Value	95% CI
Nivolumab 0.3 mg/kg	4
Nivolumab 2 mg/kg	5
Nivolumab 10 mg/kg	4

SAEs

Group	Value	95% CI
Nivolumab 0.3 mg/kg	26
Nivolumab 2 mg/kg	26
Nivolumab 10 mg/kg	22

Drug-related SAEs

Group	Value	95% CI
Nivolumab 0.3 mg/kg	3
Nivolumab 2 mg/kg	4
Nivolumab 10 mg/kg	3

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality was assessed from first dose to study completion date (up to approximately 118 months). SAEs and NSAEs were assessed from first dose to 100 days following last dose (up to approximately 79 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

NIVOLUMAB 0.3 mg/kg

Serious: 30/59 (51%)

Deaths: 51/60

NIVOLUMAB 2 mg/kg

Serious: 35/54 (65%)

Deaths: 46/54

NIVOLUMAB 10 mg/kg

Serious: 24/54 (44%)

Deaths: 47/54

Serious adverse events (130 terms)

Reaction	System	NIVOLUMAB 0.3 mg/kg	NIVOLUMAB 2 mg/kg	NIVOLUMAB 10 mg/kg
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Spinal cord compression	Nervous system disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Hypercalcaemia	Metabolism and nutrition disorders	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Pain	General disorders	—	—	—
Pyrexia	General disorders	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Paraesthesia	Nervous system disorders	—	—	—
Seizure	Nervous system disorders	—	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—

Other adverse events (105 terms — click to expand)

Reaction	System	NIVOLUMAB 0.3 mg/kg	NIVOLUMAB 2 mg/kg	NIVOLUMAB 10 mg/kg
Fatigue	General disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Pyrexia	General disorders	—	—	—
Hypersensitivity	Immune system disorders	—	—	—
Weight decreased	Investigations	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—
Chills	General disorders	—	—	—
Sinusitis	Infections and infestations	—	—	—
Blood creatinine increased	Investigations	—	—	—
Weight increased	Investigations	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—

Most-reported serious reactions: Malignant neoplasm progression, Spinal cord compression, Anaemia, Pneumonia, Hypercalcaemia, Acute kidney injury, Dyspnoea, Pulmonary embolism.

Data from ClinicalTrials.gov NCT01354431 adverse events section.

Sponsor's own description

The purpose of this study is to measure how active BMS-936558 (nivolumab) is against Renal Cell Carcinoma (RCC) as measured by the disease not progressing and whether a dose response relationship exists.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
   Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, et al · · 2012 · cited 9851× · PMID 22658127 · DOI 10.1056/nejmoa1200690
2. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.
   Motzer RJ, Rini BI, McDermott DF, Redman BG, et al · · 2015 · cited 843× · PMID 25452452 · DOI 10.1200/jco.2014.59.0703
3. Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma.
   Braun DA, Hou Y, Bakouny Z, Ficial M, et al · · 2020 · cited 771× · PMID 32472114 · DOI 10.1038/s41591-020-0839-y
4. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway.
   Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, et al · · 2015 · cited 651× · PMID 25440090 · DOI 10.1016/j.molmed.2014.10.009
5. Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors.
   Yi M, Jiao D, Xu H, Liu Q, et al · · 2018 · cited 594× · PMID 30139382 · DOI 10.1186/s12943-018-0864-3
6. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer.
   Sznol M, Chen L. · · 2013 · cited 418× · PMID 23460533 · DOI 10.1158/1078-0432.ccr-12-2063
7. Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer.
   Drake CG, Lipson EJ, Brahmer JR. · · 2014 · cited 313× · PMID 24247168 · DOI 10.1038/nrclinonc.2013.208
8. Antibody-based immunotherapy of cancer.
   Weiner LM, Murray JC, Shuptrine CW. · · 2012 · cited 204× · PMID 22424219 · DOI 10.1016/j.cell.2012.02.034