NCT04439214

Testing Nivolumab as a Potential Targeted Treatment in Cancers With Mismatch Repair Deficiency (MATCH-Subprotocol Z1D)

Completed Phase 2 Results posted Last updated 6 April 2021

What this trial tests

Phase 2 trial testing Nivolumab in Advanced Lymphoma in 47 participants. Completed in 17 May 2020.

Timeline

31 May 2016

Primary endpoint
11 October 2018

17 May 2020

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	47
Start date	31 May 2016
Primary completion	11 October 2018
Estimated completion	17 May 2020
Sites	1 location across United States

Drugs / interventions tested

• Nivolumab (nivolumab) — full drug profile →

Conditions studied

• Advanced Lymphoma — all drugs for Advanced Lymphoma →
• Advanced Malignant Solid Neoplasm — all drugs for Advanced Malignant Solid Neoplasm →
• Hematopoietic and Lymphoid Cell Neoplasm — all drugs for Hematopoietic and Lymphoid Cell Neoplasm →
• Refractory Lymphoma — all drugs for Refractory Lymphoma →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Advanced Lymphoma or Advanced Malignant Solid Neoplasm. 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.

Overall Response Rate (ORR) Primary · assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression

Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The 90% two-sided binomial exact confidence interval was calculated for ORR.

Group	Value	95% CI
Treatment (Nivolumab)	35.7	23.5 – 49.5

6-month Progression-free Survival (PFS) Rate Secondary · assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression

PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. The 6-month PFS rate was estimated using the Kaplan-Meier method which can provide a point estimate for any specific time point. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.

Group	Value	95% CI
Treatment (Nivolumab)	51.3	38.2 – 64.5

Progression-free Survival (PFS) Secondary · assessed at baseline, then every 8 weeks for the first 2 years, then every 12 weeks in year 3, until disease progression

PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients.

Group	Value	95% CI
Treatment (Nivolumab)	6.3	3.4 – 13.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Nivolumab)

Serious: 20/46 (43%)

Deaths: 24/47

Serious adverse events (31 terms)

Reaction	System	Treatment (Nivolumab)
Anemia	Blood and lymphatic system disorders	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—
Dehydration	Metabolism and nutrition disorders	—
Fatigue	General disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Sepsis	Infections and infestations	—
Skin infection	Infections and infestations	—
Creatinine increased	Investigations	—
Hyperglycemia	Metabolism and nutrition disorders	—
Nausea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Fall	Injury, poisoning and procedural complications	—
Alanine aminotransferase increased	Investigations	—
Alkaline phosphatase increased	Investigations	—
Ejection fraction decreased	Investigations	—
Weight gain	Investigations	—
Hypocalcemia	Metabolism and nutrition disorders	—
Hypokalemia	Metabolism and nutrition disorders	—
Hyponatremia	Metabolism and nutrition disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Flank pain	Musculoskeletal and connective tissue disorders	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—
Encephalopathy	Nervous system disorders	—
Myelitis	Nervous system disorders	—
Adult respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (30 terms — click to expand)

Reaction	System	Treatment (Nivolumab)
Fatigue	General disorders	—
Anemia	Blood and lymphatic system disorders	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—
Hypoalbuminemia	Metabolism and nutrition disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Hyperthyroidism	Endocrine disorders	—
Hypothyroidism	Endocrine disorders	—
Anorexia	Metabolism and nutrition disorders	—
Hypomagnesemia	Metabolism and nutrition disorders	—
Diarrhea	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Aspartate aminotransferase increased	Investigations	—
Lymphocyte count decreased	Investigations	—
Platelet count decreased	Investigations	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Alkaline phosphatase increased	Investigations	—
Hyponatremia	Metabolism and nutrition disorders	—
Dizziness	Nervous system disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Hot flashes	Vascular disorders	—
Edema limbs	General disorders	—
Alanine aminotransferase increased	Investigations	—
Creatinine increased	Investigations	—
White blood cell decreased	Investigations	—
Investigations - Other, specify	Investigations	—
Hyperglycemia	Metabolism and nutrition disorders	—
Metabolism and nutrition disorders - Other, specify	Metabolism and nutrition disorders	—
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	—
Myalgia	Musculoskeletal and connective tissue disorders	—

Most-reported serious reactions: Anemia, Rash maculo-papular, Dehydration, Fatigue, Pruritus, Sepsis, Skin infection, Creatinine increased.

Data from ClinicalTrials.gov NCT04439214 adverse events section.

Sponsor's own description

This phase II MATCH treatment trial identifies the effects of nivolumab in patients whose cancer has a genetic change called mismatch repair deficiency. Mismatch repair deficiency refers to cells that have mutations (changes) in certain genes that are involved in correcting mistakes made when DNA is copied in a cell. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells with mismatch repair deficiency to grow and spread. Researchers hope to learn if nivolumab will shrink this type of cancer or stop its growth.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.