RECRUITING

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in Melanoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This research study is studying the drugs called NeoVax (a new type of personalized neoantigen vaccine) in combination with CDX-301 and Nivolumab or Pembrolizumab as a possible treatment for melanoma. The names of the study drugs involved in this study are: * Personalized Neoantigen peptides (which combined with poly-ICLC make the vaccine NeoVax) * Poly-ICLC (Hiltonol) * CDX-301 * Nivolumab (Opdivo) * Pembrolizumab (Keytruda)

Official Title

A Phase Ib Study of NeoVax in Combination With CDX-301 and Nivolumab or Pembrolizumab and in Patients With Melanoma

Quick Facts

Study Start:2022-01-03

Study Completion:2027-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04930783

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Inclusion Criteria * Participant is willing and able to give written informed consent * Participants must have histologically confirmed stage IIIB/C/D or stage IV cutaneous melanoma (mucosal melanoma or uveal melanoma are excluded) that is surgically resected, is deemed surgically resectable, or is unresectable; tumor tissue for sequence analysis must be available from either previous melanoma resection/biopsy or at least one site of disease must be amenable to surgical or core biopsy * Age ≥ 18 years * ECOG performance status of 0 or 1 * Recovered from all toxicities associated with prior treatment, to acceptable baseline status (as to Lab toxicity see below limits for inclusion) or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, Grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo * Participants must have normal organ and marrow function as defined below: * WBC ≥3,000/µL * ANC ≥1,500/µL * Platelets ≥100,000/µL * Hemoglobin ˃ 9.0 g/dL * Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) * AST(SGOT)/ALT(SGPT) ≤ 3 x ULN * Creatinine ≤ 1.5 x ULN OR * Creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (if using the Cockcroft-Gault formula below): * Women of childbearing potential (WOCBP) should have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab or Pembrolizumab, because the effects of NeoVax plus Montanide and Nivolumab (or Pembrolizumab) on the developing human fetus are unknown * Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated Nivolumab or Pembrolizumab, Personalized Neoantigen vaccine, and CDX-301 * Female participants enrolled in the study, who are not free from menses for \>2 years, post hysterectomy / oophorectomy, or surgically sterilized, should be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 5 months after the last dose of study therapy. Approved contraceptive methods include for example: intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.The investigational product will be permanently discontinued in an appropriate manner. * Male participants should agree to use an adequate method of contraception starting with visit 1 through 7 months after the last dose of study therapy	* Prior immunotherapy for metastatic melanoma except for anti-CTLA-4. Patients with unresectable melanoma who have received PD-1 inhibition therapy as adjuvant therapy and stopped receiving PD-1 inhibition for a period of ≥ 6 months before starting treatment with Nivolumab or Pembrolizumab are allowed to participate. * Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents including but not limited to methotrexate, chloroquine, azathioprine, etc. within six months of study participation * Active brain metastases or leptomeningeal metastases * Use of a non-oncology vaccine therapy for prevention of infectious diseases (with the exception of vaccination against the SARS-CoV-2 virus for the prevention of COVID-19 disease) during the 4 week period prior to first dose of Nivolumab or Pembrolizumab. * History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases * 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 * 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. Corticosteroids used as pre-medication for imaging studies are allowed. * Test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection * Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). * Known sensitivity or allergy to Nivolumab, Pembrolizumab, or CDX-301 * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic * Any underlying medical condition, psychiatric condition or social situation that in the opinion of the investigator would compromise study administration as per protocol or compromise the assessment of AEs * Planned major surgery (except for surgery for resection of melanoma if applicable). * Patients with known mutations/amplifications in Flt-3 * Pregnant women are excluded from this study because Nivolumab, personalized neoantigen peptides and poly-ICLC are agents with unknown risks to the developing fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with Nivolumab, personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study * Individuals with a history of an invasive malignancy are ineligible except for the following circumstances: a) individuals with a history of invasive malignancy are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with the following cancers are eligible if diagnosed and treated - carcinoma in situ of the breast, oral cavity or cervix, localized prostate cancer, basal cell or squamous cell carcinoma of the skin * Prisoners, or subjects who are compulsory detained are not eligible to participate

Inclusion Criteria

Exclusion Criteria

* Inclusion Criteria
* Participant is willing and able to give written informed consent
* Participants must have histologically confirmed stage IIIB/C/D or stage IV cutaneous melanoma (mucosal melanoma or uveal melanoma are excluded) that is surgically resected, is deemed surgically resectable, or is unresectable; tumor tissue for sequence analysis must be available from either previous melanoma resection/biopsy or at least one site of disease must be amenable to surgical or core biopsy
* Age ≥ 18 years
* ECOG performance status of 0 or 1
* Recovered from all toxicities associated with prior treatment, to acceptable baseline status (as to Lab toxicity see below limits for inclusion) or a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, Grade of 0 or 1, except for toxicities not considered a safety risk, such as alopecia or vitiligo
* Participants must have normal organ and marrow function as defined below:
* WBC ≥3,000/µL
* ANC ≥1,500/µL
* Platelets ≥100,000/µL
* Hemoglobin ˃ 9.0 g/dL
* Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
* AST(SGOT)/ALT(SGPT) ≤ 3 x ULN
* Creatinine ≤ 1.5 x ULN OR
* Creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (if using the Cockcroft-Gault formula below):
* Women of childbearing potential (WOCBP) should have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Nivolumab or Pembrolizumab, because the effects of NeoVax plus Montanide and Nivolumab (or Pembrolizumab) on the developing human fetus are unknown
* Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated Nivolumab or Pembrolizumab, Personalized Neoantigen vaccine, and CDX-301
* Female participants enrolled in the study, who are not free from menses for \>2 years, post hysterectomy / oophorectomy, or surgically sterilized, should be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity throughout the study, starting with visit 1 through 5 months after the last dose of study therapy. Approved contraceptive methods include for example: intra uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.The investigational product will be permanently discontinued in an appropriate manner.
* Male participants should agree to use an adequate method of contraception starting with visit 1 through 7 months after the last dose of study therapy

* Prior immunotherapy for metastatic melanoma except for anti-CTLA-4. Patients with unresectable melanoma who have received PD-1 inhibition therapy as adjuvant therapy and stopped receiving PD-1 inhibition for a period of ≥ 6 months before starting treatment with Nivolumab or Pembrolizumab are allowed to participate.
* Concomitant therapy with any anti-cancer agents, other investigational anti-cancer therapies, or immunosuppressive agents including but not limited to methotrexate, chloroquine, azathioprine, etc. within six months of study participation
* Active brain metastases or leptomeningeal metastases
* Use of a non-oncology vaccine therapy for prevention of infectious diseases (with the exception of vaccination against the SARS-CoV-2 virus for the prevention of COVID-19 disease) during the 4 week period prior to first dose of Nivolumab or Pembrolizumab.
* History of severe allergic reactions attributed to any vaccine therapy for the prevention of infectious diseases
* 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
* 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. Corticosteroids used as pre-medication for imaging studies are allowed.
* Test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
* Known sensitivity or allergy to Nivolumab, Pembrolizumab, or CDX-301
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring treatment, symptomatic
* Any underlying medical condition, psychiatric condition or social situation that in the opinion of the investigator would compromise study administration as per protocol or compromise the assessment of AEs
* Planned major surgery (except for surgery for resection of melanoma if applicable).
* Patients with known mutations/amplifications in Flt-3
* Pregnant women are excluded from this study because Nivolumab, personalized neoantigen peptides and poly-ICLC are agents with unknown risks to the developing fetus. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with Nivolumab, personalized neoantigen peptides and poly-ICLC, nursing women are excluded from this study
* Individuals with a history of an invasive malignancy are ineligible except for the following circumstances: a) individuals with a history of invasive malignancy are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy; b) individuals with the following cancers are eligible if diagnosed and treated - carcinoma in situ of the breast, oral cavity or cervix, localized prostate cancer, basal cell or squamous cell carcinoma of the skin
* Prisoners, or subjects who are compulsory detained are not eligible to participate

Contacts and Locations

Study Contact

Patrick A Ott, MD, PhD

CONTACT

(617) 632-5055

patrick_ott@dfci.harvard.edu

Principal Investigator

Patrick A Ott, MD, PhD

PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Study Locations (Sites)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

Sponsor: Dana-Farber Cancer Institute

Patrick A Ott, MD, PhD, PRINCIPAL_INVESTIGATOR, Dana-Farber Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-01-03

Study Completion Date2027-01-31

Study Record Updates

Study Start Date2022-01-03

Study Completion Date2027-01-31

Terms related to this study

Keywords Provided by Researchers

Melanoma
Metastatic Melanoma

Additional Relevant MeSH Terms

Melanoma
Metastatic Melanoma