Clinical Trials /

Study of Safety and Tolerability of Nivolumab Treatment Alone or in Combination With Relatlimab or Ipilimumab in Head and Neck Cancer

NCT04080804

Description:

The aim of this study is to potentiate adaptive immunity to enhance the anti-tumor activity of anti-PD1 antibody by the addition of anti-CTLA4 antibody or anti-LAG3 antibody (relatlimab) given in subjects with resectable locally advanced HNSCC prior to surgical resection.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Safety and Tolerability of Nivolumab Treatment Alone or in Combination With Relatlimab or Ipilimumab in Head and Neck Cancer
  • Official Title: A Phase II Neoadjuvant Study of the Safety and Tolerability of Anti-PD1 (Nivolumab) Administered Alone or in Combination With Anti-LAG3 (Relatlimab) or Anti-CTLA4 (Ipilimumab) in Resectable Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: HCC 18-139
  • SECONDARY ID: CA224-056
  • NCT ID: NCT04080804

Conditions

  • Head and Neck Squamous Cell Carcinoma (HNSCC)

Interventions

DrugSynonymsArms
Nivolumabanti-PD-1 antibody, OPDIVO®Nivolumab + Relatlimab
Relatlimabanti-LAG3 antibody, BMS-986016Nivolumab + Relatlimab
Ipilimumabanti-CTLA4 antibody, Yervoy ®Nivolumab + Ipilimumab

Purpose

It is anticipated that anti-PD-1 antibody (nivolumab), administered as a single agent or in combination with anti-CTLA-4 antibody (ipilimumab), or anti-LAG-3 antibody (BMS-986016) will demonstrate adequate safety and tolerability, as well as a favorable risk/benefit profile, to support further clinical testing in head and neck squamous cell carcinoma (HNSCC). Correlative biomarker hypotheses will be evaluated using pre- and post-treatment tissue specimens. The aim of this study is to potentiate adaptive immunity to enhance the anti-tumor activity of anti-PD1 antibody by the addition of anti-CTLA4 antibody or anti-LAG3 antibody (relatlimab) given in subjects with resectable locally advanced HNSCC prior to surgical resection.

Detailed Description

      Immunotherapeutic agents have been well tolerated in the recurrent/metastatic patient
      population. Studies have shown that delay of surgical resection for 3-4 weeks after diagnosis
      is acceptable. Overall survival for locally advanced head and neck squamous cell carcinoma
      are poor with the current treatment modalities available. Previously untreated, locally
      advanced (AJCC 8th edition stage III-IVa) HPV+ and HPV- head and neck squamous cell carcinoma
      patients who are candidates for surgical resection, as deemed by the multidisciplinary team
      will be included in this trial. Patients with histories of autoimmune disease or with current
      or previous histories of immune modulating agents will be excluded from participation.
      Relatlimab will be given IV at a dose of 160 mg IV on D1 (and on D28 if surgery is postponed
      at the discretion of the investigator). Nivolumab will be given IV at a dose of 480 mg on D1
      (and on D28 if surgery is postponed at the discretion of the investigator) when given alone
      or with relatlimab. Nivolumab will be given at dose of 3mg/kgIV every 2 weeks on D1 and D14
      (and on D28 if the operating room time is not yet available, and the 4 week CT scan
      demonstrates at least stable disease ) when given with Ipilimumab. Ipilimumab will be given
      at a dose of 1 mg/kg IV once only on D1. Patients will undergo biopsy and CT scan prior to
      treatment initiation. 4 weeks (+/- 1 week) after, patient will undergo surgical resection. CT
      scan will be repeated prior to surgery (from 1-72 hours prior to surgery). The patients will
      be monitored from time of biopsy until 6 months postoperatively.
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab + RelatlimabExperimental20 patients at Nivolumab 480mg IV + Relatlimab 160mg IV D1 - optional Nivolumab 480 mg IV + Relatlimab 160mg IV D28 (D28 at clinician discretion i.e. surgery postponed)
  • Nivolumab
  • Relatlimab
Nivolumab + IpilimumabExperimental20 patients at Nivolumab 240 mg IV + Ipilimumab 1mg/kg D1 then Nivolumab 240 mg D14 and then optional Nivolumab 240 mg D28 (D28 at clinician discretion i.e. surgery postponed)
  • Nivolumab
  • Ipilimumab
NivolumabExperimental20 patients Nivo 480 mg IV D1 and then optional Nivo 480 mg IV D28 (D28 clinician discretion i.e. surgery postponed)
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          1. Males and females, ages ≥18 years

          2. Histologically or cytologically confirmed Squamous Cell Carcinoma, previously
             untreated stage III, or IVA HNC by AJCC 8th edition staging system. For HPV positive
             oropharyngeal cancer, patients with T3 or T4 primary and/or one ipsilateral lymph node
             greater than 3 cm, multiple ipsilateral lymph nodes, bilateral lymph nodes, or
             contralateral lymph node will be included. Patients must undergo CT or MRI to rule out
             the presence of distant metastases.

          3. Accessible tumor for pretreatment (baseline) open/incisional biopsy to provide
             adequate correlative specimen.

          4. Have LAG-3 and PD-L1 results for stratification.

          5. LVEF assessment with documented LVEF ≥50% by either TTE or MUGA (TTE preferred test)
             within 6 months from first study drug administration

          6. Women of child-bearing potential (WOCBP) must be advised of the importance of avoiding
             pregnancy during trial participation and the potential risk factors for an
             unintentional pregnancy. All WOCBP MUST have a negative pregnancy test within 7 days
             prior to first receiving investigational product. If the pregnancy test is positive,
             the patient must not receive investigational product and must not be enrolled in the
             study. Conduct a pregnancy test within 24 hours of study drug administration as part
             of the safety monitoring. All WOCBP must agree to use appropriate contraception to
             prevent pregnancy for the duration of treatment with study treatments, plus 24 weeks
             after the last dose of study treatment (i.e., 30 days [duration of ovulatory cycle]
             plus approximately 5 half-lives).

          7. All males must agree to use appropriate contraception for the duration of treatment
             with study treatments plus 33 weeks after the last dose of study treatment (i.e., 90
             days [duration of sperm turnover] plus approximately 5 half-lives). In addition, male
             participants must be willing to refrain from sperm donation during this time. In
             addition, men enrolled on this study must be informed of the risks to any sexual
             partner of childbearing potential and should practice an effective method of birth
             control

          8. Azoospermic males are exempt from contraceptive requirements unless the potential
             exists for fetal toxicity due to study drug being present in seminal fluid, even if
             the participant has undergone a successful vasectomy or if the partner is pregnant.
             WOCBP who are continuously not heterosexually active are also exempt from
             contraceptive requirements, and still must undergo pregnancy testing as described in
             this section.

          9. Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be
             included.

         10. Eligible for surgical resection.

         11. Age ≥ 18 years

         12. ECOG performance status 0-1.

         13. Have signed written informed consent

        Exclusion Criteria:

          1. Prior radiation, chemotherapy, or immunotherapy.

          2. Prior severe infusion reaction to a monoclonal antibody.

          3. Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Subjects with TnT or TnI levels
             between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are less
             than or equal to 1 x ULN. If TnT or TnI levels are > 1 to 2 × ULN within 24 hours, the
             subject may undergo a cardiac evaluation and be considered for treatment, following a
             discussion with the BMS Medical Monitor or designee. When repeat levels within 24
             hours are not available, a repeat test should be conducted as soon as possible. If TnT
             or TnI repeat levels beyond 24 hours are < 2 x ULN, the subject may undergo a cardiac
             evaluation and be considered for treatment.

          4. Evidence of distant metastasis.

          5. Prior history of HNC treated < 5 years previously.

          6. Prior history of myocarditis, regardless of etiology

          7. Prior treatment with LAG-3 targeted agents.

          8. Prior oncology vaccine therapy or immunotherapy agents.

          9. Hepatitis B or C

         10. Patients with active/history of autoimmune disease. "Active" refers to any condition
             currently requiring therapy. Examples of autoimmune disease include systemic lupus
             erythematosus, multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis

         11. Psychiatric illness or other social issues limiting compliance

         12. If second primary tumor is found at the time of EUA, the subject will be excluded from
             study participation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events related to treatment of nivolumab in combination with relatlimab
Time Frame:Up to 4 months
Safety Issue:
Description:Number of participants experiencing adverse events related to treatment with nivolumab in combination with relatlimab per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Secondary Outcome Measures

Measure:Pathologic response
Time Frame:Up to 2 months (prior to treatment and day of surgery)
Safety Issue:
Description:Response to treatment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Robert Ferris

Trial Keywords

  • anti-PD1 antibody
  • anti-CTLA4 antibody
  • anti-LAG3 antibody
  • tumor infiltrating lymphocyte (TIL)

Last Updated