Nivolumab Plus Ipilimumab in Thyroid Cancer

NCT03246958 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-255
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for thyroid cancer. The drugs involved in this study are:

• Nivolumab (Opdivo™)
• Ipilimumab (Yervoy™)

Conditions

Thyroid Cancer

Keywords

Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate

  Best overall response rate is defined as the percentage of participants who achieved Complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  Median (range) treatment duration (days) of 163.0 (21.0-734.0) for DTC cohort, for MTC cohort was 58.0 (30.0-252.0), and for ATC cohort 135.5 (10.0-735.0).

Secondary Outcomes (3)

• Median Progression Free Survival

  Median (range) follow-up (months) for DTC cohort was 24.0 (1.84 - 24.7), for MTC cohort was 24.0 (23.0-24.2), and for ATC cohort was 22.2 (0.46 - 26.1).

• Overall Survival at 2 Years (OS2)

  Median (range) follow-up (months) for DTC cohort was 24.0 (1.84 - 24.7), for MTC cohort was 24.0 (23.0-24.2), and for ATC cohort was 22.2 (0.46 - 26.1).

• Treatment-Related Adverse Events Rate

  AEs were assessed every two weeks on treatment and within 30 days after the last dose. Median (range) treatment duration (days) of 163.0 (21.0-734.0) for DTC cohort, for MTC cohort was 58.0 (30.0-252.0), and for ATC cohort 135.5 (10.0-735.0).

Study Arms (10)

DTC - Nivolumab alone for two weeks

EXPERIMENTAL

Differentiated Thyroid Cancer (DTC) participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

DTC - Ipilimumab alone for two weeks

EXPERIMENTAL

Differentiated Thyroid Cancer (DTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

Differentiated Thyroid Cancer (Primary cohort)

EXPERIMENTAL

Differentiated Thyroid Cancer (DTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.

Drug: Nivolumab; Drug: Ipilimumab

Medullary Thyroid Cancer (Exploratory Cohort)

EXPERIMENTAL

Medullary Thyroid Cancer (MTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second, or started Ipi or Nivo together. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.

Drug: Nivolumab; Drug: Ipilimumab

Anaplastic Thyroid Cancer (Exploratory Cohort)

EXPERIMENTAL

Anaplastic Thyroid Cancer (ATC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second prior to study amendment or in combination from the start after study amendment due to aggressive nature of the disease in this cohort. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.

Drug: Nivolumab; Drug: Ipilimumab

MTC - Nivolumab alone for two week

EXPERIMENTAL

Medullary Thyroid Cancer (MTC)participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

MTC - Ipilimumab alone for two weeks

EXPERIMENTAL

Medullary Thyroid Cancer (MTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

ATC - Nivolumab alone for two week

EXPERIMENTAL

Anaplastic Thyroid Cancer (ATC) received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

ATC - Ipilimumab alone for two week

EXPERIMENTAL

Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.

Drug: Nivolumab; Drug: Ipilimumab

ATC - Ipilimumab + Nivolumab

EXPERIMENTAL

Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks and Ipilimumab 1mg/kg q6 weeks via IV infusion.

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Ipilimumab are types of immunotherapy Immunotherapy works by encouraging the body's own immune system to attack cancer cells.

Also known as: Opdivo

ATC - Ipilimumab + Nivolumab; ATC - Ipilimumab alone for two week; ATC - Nivolumab alone for two week; Anaplastic Thyroid Cancer (Exploratory Cohort); DTC - Ipilimumab alone for two weeks; DTC - Nivolumab alone for two weeks; Differentiated Thyroid Cancer (Primary cohort); MTC - Ipilimumab alone for two weeks; MTC - Nivolumab alone for two week; Medullary Thyroid Cancer (Exploratory Cohort)

Ipilimumab DRUG

Nivolumab are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack cancer cells.

Also known as: Yervoy

ATC - Ipilimumab + Nivolumab; ATC - Ipilimumab alone for two week; ATC - Nivolumab alone for two week; Anaplastic Thyroid Cancer (Exploratory Cohort); DTC - Ipilimumab alone for two weeks; DTC - Nivolumab alone for two weeks; Differentiated Thyroid Cancer (Primary cohort); MTC - Ipilimumab alone for two weeks; MTC - Nivolumab alone for two week; Medullary Thyroid Cancer (Exploratory Cohort)

Eligibility Criteria

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

You may qualify if:

• Metastatic, RAI refractory, differentiated thyroid cancer (including papillary and follicular thyroid cancer and their sub-types such as Hurthle cell thyroid cancer as well as poorly differentiated thyroid cancer), with progression within 13 months prior to study registration. RAI refractoriness is defined as absence of uptake of RAI on either a low-dose diagnostic test or a post-treatment RAI scan in measurable lesions or radiographic progression of disease within 12 months of the last course of RAI treatment despite the recorded uptake of RAI with that previous therapy or having a cumulative lifetime administered dose of greater than 600mCi.
• Exploratory cohort: incurable medullary thyroid cancer with prior tyrosine kinase inhibitor (TKI) failure and progression within 13 months prior to enrollment (10 patients) and anaplastic thyroid cancer (7 patients)
• Any number of lines of prior treatment are allowed
• Any line of prior treatment for patients under 65y, over 65y must have at least one prior line of TKI treatment
• Age 18 years or older
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Participants must have normal organ and marrow function as defined below:
• Screening laboratory values must meet the following criteria and should be obtained within 21 days prior to randomization/registration
• WBC ≥ 2000/μL
• Neutrophils ≥ 1500/μL
• Platelets ≥ 100 x103/μL
• Hemoglobin \> 9.0 g/dL
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
• Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
• Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

You may not qualify if:

• Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients who are receiving any other investigational agents.
• Patients with activebrain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Sehgal K, Pappa T, Shin KY, Schiantarelli J, Liu M, Ricker C, Besson NR, Jones SM, Welsh EL, Pfaff KL, Barletta JA, Park J, Reardon B, Doherty GM, Alexander EK, Rodig SJ, Barbie DA, O'Neill A, Van Allen E, Haddad RI, Lorch JH. Dual Immune Checkpoint Inhibition in Patients With Aggressive Thyroid Carcinoma: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2024 Dec 1;10(12):1663-1671. doi: 10.1001/jamaoncol.2024.4019.

  PMID: 39446365 DERIVED

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Limited number of patients accrued into ATC and MTC cohort.

Results Point of Contact

• Title: Dr. Kartik Sehgal
• Organization: Dana Farber Cancer Institute (DFCI)

kartik_sehgal@dfci.harvard.edu

617-632-3090

Study Officials

• Kartik Sehgal, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Kartik Sehgal, MD

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 11, 2017
• Study Start: October 3, 2017
• Primary Completion: January 21, 2021
• Study Completion: July 31, 2021
• Last Updated: June 19, 2025
• Results First Posted: May 21, 2024

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)