Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Neoplasm Metastasis

Recurrence

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Nivolumab

Ipilimumab

Relatlimab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Nivolumab will be dosed 480mg IV q 4 weeks and Relatlimab 160mg IV q 4 weeks

One cycle is defined as 4 weeks of treatment and both drugs are given on the same day.

Patients will receive the prescribed therapy continuously for up to 24 cycles until progression of disease or adverse event(s) requiring treatment discontinuation.

Nivolumab will be dosed at 3mg/kg IV q 2 weeks and Ipilimumab 1mg/kg IV q 6 weeks.

Patients will receive four doses of Ipilimumab and the last dosage of Nivolumab 3mg/kg IV q 2 weeks will be given at the time of the 4th dose of Ipilimumab, followed 2 weeks later by Nivolumab 480 mg IV q 4 weeks. A cycle of therapy will be defined as 4 weeks of treatment. The patient will receive the prescribed therapy continuously for up to 24 cycles until progression of disease or adverse event(s) requiring treatment discontinuation.

IV administration of both Nivolumab and Relatlimab

Nivolumab+Relatlimab

IV administration of both Nivolumab and Ipilimumab

Nivolumab+Ipilimumab

Dan P Zandberg, MD

In this Phase II trial of personalized immunotherapy in R/M HNSCC, gene expression of LAG3 and CTLA4 by RNA seq will be determined to select the appropriate agent (Ipilimumab or Relatlimab) to add to Nivolumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) who have failed prior immunotherapy with anti-PD-1 or PD-L1 mAb therapy. The agent, either Ipilimumab or Relatlimab will be chosen based on the highest relevant immune gene expression (CTLA4 or LAG-3) as long as the minimum difference required is met.

In this Phase II non-randomized trial, n=40 eligible patients will have tumor tissue (core or excisional/incisional) for gene expression of LAG3 and CTLA4 via RNA seq per OmniSeq Immune Report Card to determine which drug (either Relatlimab or Ipilimumab) will be added to Nivolumab for treatment. The patient will then receive the prescribed therapy continuously for up to 24 cycles (1 cycle = 28 days). The drug to be added to Nivolumab will be based on which relevant gene has the highest expression as long as the minimum difference required is met. If the minimum difference is not met than a patient will be randomized to either Nivolumab plus Relatlimab or Nivolumab plus Ipilimumab.

The patient will then receive the prescribed therapy continuously for up to 24 cycles (1 cycle = 28 days) with repeat imaging prior to every 3rd cycle until progression of disease. Response, evaluated by RECIST 1.1, with modifications to allow for continued therapy until progressive disease is confirmed if the patient is clinically stable, will be used in the trial. If the patient has confirmed progression the patient may be eligible to undergo a second biopsy and second treatment on trial. If these criteria are met the patient will then be treated with this new combination with repeat imaging prior to every 3rd cycle as per initial treatment, until progression of disease.

In this open-label, 2 parallel arms trial, RNA seq analysis via the Omniseq immune report card will be used to determine which drug (Relatlimab or Ipilimumab) will be added to Nivolumab for treatment.

Personalized Immunotherapy in Patients With Recurrent /Metastatic SCCHN That Have Progressed on Prior Immunotherapy

A Phase II Trial of Personalized Immunotherapy in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck That Have Progressed on Prior Immunotherapy

The estimated probability of response to therapy in patients who have progressed on prior immunotherapy. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is disappearance of all target and non-target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

The estimated Disease Control Rate (DCR) in patients who have progressed on prior immunotherapy. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is disappearance of all target and non-target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Stable Disease (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions.

The length of time from the start of treatment that patients live with disease that does not progress per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in patients who have progressed on prior immunotherapy. Per RECIST, Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions compared to baseline sum of target lesions, or any new lesions.It also includes the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

The length of time from the start of treatment that patients remain alive, in patients who have progressed on prior immunotherapy.

Adverse Events possibly, probably or definitely related to study treatment per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 experienced by all patients.

Bristol-Myers Squibb

Dan Zandberg

Director, Head and Neck and Thyroid Cancer Disease Sections and Co-Director, UPMC Hillman Cancer Center Head and Neck Cancer Research Program

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma, Renal Cell

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Anti-Infective Agents

Antibodies

Lenvatinib

Everolimus

Sirolimus

Immunoglobulins

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

CMN-001 dosing (1x10\^7 DC/dose) is initiated at Visit 2 during 1st line therapy and through 2nd line therapy. CMN-001 is administered as 1 dose every 3 weeks for 3 doses (Induction phase), followed by maintenance doses, 1 every 4 weeks for 7 doses (Maintenance phase), followed by booster doses, 1 dose every 12 weeks (Booster phase). 1st line therapy, Nivolumab (3mg/kg) + Ipilimumab (1 mg/kg) will be administered at 3 week intervals for 4 administrations starting at visit 1. Followed by Nivolumab (3 mg/kg) administration every 4 weeks until progression. After progression, 2nd line therapy with lenvatinib (18mg/day) + everolimus (5mg/day) until discontinuation criteria are met.

1st line therapy, Nivolumab (3mg/kg) + Ipilimumab (1 mg/kg) will be administered at 3 week intervals for 4 administrations starting at visit 1. Followed by Nivolumab (3 mg/kg) administration every 4 weeks until progression. After progression 2nd line therapy with lenvatinib (18mg/day) + everolimus (5mg/day) until discontinuation criteria are met.

CMN-001

Lenvatinib+Everolimus

CMN-001 is an autologous, tumor antigen-loaded dendritic cell immunotherapy. The active components of CMN-001 are autologous, matured dendritic cells, which have been co-electroporated with both in vitro transcribed (IVT) RNA from an autologous tumor specimen and CD40L RNA. CMN-001 is indicated for treatment of intermediate/poor risk patients with advanced renal cell carcinoma (RCC) in combination with nivolumab plus ipilimumab as first line therapy and in combination with lenvatinib plus everolimus as 2nd line therapy post 1st line failure.

Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma

A Phase 2b Randomized Trial of Autologous Dendritic Cell Immunotherapy (CMN-001) Plus Standard Treatment of Advanced Renal Cell Carcinoma

Patients will be followed for OS until the completion of the study.

Progression-free survival from the date of subject randomization as assessed by the investigator per iRECIST.

Radiological evidence of progression will be derived from tumor imaging assessments at baseline (Screening, Week 0) and restaging scans at Week 13, 21, 29, 37 then every 12 weeks until progression or study withdrawal.

To compare tumor responses based on iRECIST between study arms

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Personalized Immunotherapy in Patients With Recurrent /Metastatic SCCHN That Have Progressed on Prior Immunotherapy	NCT04326257	Squamous Cell C...	Nivolumab+Relat... Nivolumab+Ipili...	18 Years -	University of Pittsburgh
Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma	NCT04203901	Advanced Renal ...	CMN-001 Nivolumab+Ipili... Lenvatinib+Ever...	18 Years -	CoImmune
Personalized Immunotherapy in Patients With Recurrent /Metastatic SCCHN That Have Progressed on Prior Immunotherapy	NCT04326257	Squamous Cell C...	Nivolumab+Relat... Nivolumab+Ipili...	18 Years -	University of Pittsburgh

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