A Study of a Personalized Neoantigen Cancer Vaccine

Overview

About this study

The purpose of this study is to evaluate the safety, dose, immunogenicity and early clinical activity of GRT-C901 and GRT-R902, a personalized neoantigen cancer vaccine, in combination with nivolumab and ipilimumab, in patients with metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal adenocarcinoma, and metastatic urothelial cancer.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - Vaccine Production Stage: 

  • Provide a signed and dated ICF document prior to initiation of study-specific procedures.
  • Patients with the indicated advanced or metastatic solid tumor as follows:
    • NSCLC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy (note: patients receiving anti-PD-(L)1 monotherapy are eligible);
    • GEA who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy;
    • mUC who are planned for or have received no more than 1 cycle of systemic treatment with cytotoxic, platinum-based chemotherapy;
    • CRC-MSS who are receiving first line systemic therapy or who are planned for or have received no more than 1 cycle of second line systemic therapy including a fluoropyrimidine and oxaliplatin or irinotecan.
  • Availability of FFPE tumor specimen for neoantigen assessment.
  • Measurable disease according to RECIST v1.1.
  • Lesions amenable to biopsy.
  • ≥ 12 years of age (patients 12–17 years of age must weigh > 40 kg).
  • Life expectancy of > 6 months per the investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (or equivalent for patients 12–17 years of age based on Karnofsky or Lansky performance scale. 
  • Patient has adequate organ function using values obtained within 4 weeks prior to starting routine therapy as defined below. The Sponsor may consider patients eligible despite having a laboratory value that does not meet inclusion criteria provided the Investigator reports the patient is otherwise in good health and the history and kinetics of the change in the laboratory value do not raise a significant safety concern over including the patient in the study nor compromise the integrity of the study data. The Sponsor and Investigator must agree to include any patients with a laboratory value below the defined criteria below:
    • Peripheral white blood cell (WBC) ≥ 3000/mm^3;
    • Absolute lymphocyte count (ALC) ≥ 800/mm^3;
    • Absolute neutrophils count (ANC) ≥ 1500/mm^3;
    • Platelets ≥ 100,000/mm^3;
    • Hemoglobin ≥ 9 g/dL;
    • Albumin ≥ 3 g/dL;
    • Calculated creatinine clearance > 50 mL/min using Cockcroft-Gault equation;
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN;
    • Total bilirubin ≤ 1.5 × ULN OR direct bilirubin ≤ 1 × ULN (patients with Gilbert’s disease may be included if their total bilirubin is ≤ 3.0 mg/dL);
    • International normalized ratio (INR) or prothrombin time (PT) or partial thromboplastin time (PTT) ≤ 1.5 × ULN.
  • For NSCLC only, a history of smoking, defined as more than 5 packs, or 100 lifetime cigarettes.
  • If women of childbearing potential (WCBP), willing to undergo pregnancy testing and agrees to use at least 1 highly effective contraceptive method during the study treatment period and for 5 months after last investigational study treatment.
  • Eligibility assessments outlined above may be waived by the Sponsor for patients who were enrolled and eligible for the Vaccine Production Stage under the separate Gritstone sponsored protocol GO-003.

Inclusion Criteria - Study Treatment Stage:

  • If patient did not participate in the Vaccine Production part of this study, patient has been enrolled in the screening protocol GO-003.
  • Provide a signed and dated ICF document prior to initiation of any treatment-related study-specific procedures.
  • Patient has received routine therapy as follows:
  • Patient with NSCLC, mUC, or GEA who has received systemic treatment with cytotoxic, platinum-based chemotherapy, has measurable disease according to RECIST v1.1; and 
  • has chemotherapy and has an assessment of stable disease, partial response, or complete response: will either receive study treatment in addition to continued routine therapy, or will receive study treatment after stopping routine therapy, per Investigator discretion; OR
  • has experienced disease progression: will receive study treatment as next line of therapy (i.e., without chemotherapy); OR
  • is intolerant to chemotherapy: will receive study treatment as next line of therapy (i.e., without chemotherapy);
  • Patient with CRC-MSS who has received second-line systemic therapy including a fluoropyrimidine and oxaliplatin or irinotecan, has measurable disease according to RECIST v1.1, and:
  • has assessment of stable disease, partial response, or complete response: will receive study treatment in addition to continued routine therapy per Investigator discretion; OR
  • has experienced disease progression: will receive study treatment as next line of therapy; OR
  • is intolerant to chemotherapy: will receive study treatment as next line of therapy.
  • Patient agrees to undergo research biopsies prior to study treatment and approximately 16 weeks after first vaccine administration (if patient has lesions amenable to biopsy).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (or equivalent for patients 12–17 years of age based on Karnofsky or Lansky performance scale. 
  • Patient has adequate organ function as defined below. The Sponsor may consider patients eligible despite having a laboratory value that does not meet inclusion criteria provided the Investigator reports the patient is otherwise in good health and the history and kinetics of the change in the laboratory value do not raise a significant safety concern over including the patient in the study nor compromise the integrity of the study data. The Sponsor and Investigator must agree to include any patients with a laboratory value below the defined criteria below:
    • Peripheral WBC ≥ 2000/mm^3;
    • ALC ≥ 500/ mm^3;
    • ANC ≥ 1000/mm^3;
    • Platelets ≥ 75000/mm^3;
    • Hemoglobin ≥ 9 g/dL;
    • Calculated creatinine clearance > 40 mL/min using Cockcroft-Gault equation;
    • ALT and AST ≤ 3 × ULN unless liver metastases are present in which case patients are included; if ALT and AST ≤ 5 × ULN;
    • Total bilirubin ≤ 1.5 × ULN; OR direct bilirubin ≤ 1 × ULN (patients with Gilbert's disease may be included if their total bilirubin is ≤ 3.0 mg/dL).
    • INR and PT and PTT ≤ 1.5 × ULN, unless patient is receiving anti-coagulant therapy in which case patients are eligible if PT and PTT is within therapeutic range of intended use of anti-coagulants.

Exclusion Criteria - Vaccine Production Stage:

  • Tumors with genetic characteristics as follows:
    • For NSCLC, patients with a known genetic driver alteration in EGFR, ALK, ROS1, RET, or TRK;
    • For  CRC and GEA, patients with known MSIhi disease based on institutional standard;
    • For CRC, patients with a known BRAF V600E mutation or patients with peritoneal carcinomatosis and for GEA, patients with peritoneal carcinomatosis as their only evidence of disease
  • Patient has a known tumor mutation burden < 1 non-synonymous mutations/MB.
  • Known exposure to chimpanzee adenovirus or any history of anaphylaxis in reaction to a vaccination or allergy or hypersensitivity to study drug components.
  • Bleeding disorder (e.g., factor deficiency, coagulopathy) or history of significant bruising or bleeding following IM injections or blood draws.
  • Patient has received prior therapy consisting of anti-CTLA-4, anti-PD-1, anti-PD-L1, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
    • Note: Patients with NSCLC and GEA who have been, or are currently being, treated with anti-PD-(L)1 monotherapy are eligible.
  • Immunosuppression that is expected to be present at the time of study treatment after vaccine production and coming from:
    • Concurrent, recent (≤ 4 weeks) or anticipated treatment with systemic corticosteroids (>10 mg daily prednisone equivalent), or other immunosuppressive medications such as OKT3, ATG/ALG, methotrexate, tacrolimus, cyclosporine, azathioprine or rapamycin. Inhaled or topical steroids, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, steroid pre-treatment for chemotherapy (eg, pemetrexed), antihistamines, non-steroidal anti-inflammatory drugs, and aspirin are permitted in the absence of active autoimmune disease;
    • Conditions such as common variable hypogammaglobulinemia or radiation exposure such as large field radiotherapy.
  • History of allogeneic tissue/solid organ transplant.
  • Patients who have had a history of life-threatening treatment-related AEs with prior immunotherapy or have not recovered from prior cancer therapy-induced AEs (i.e., any AE that remains ≥ Grade 2, or that has not returned to baseline with the exception of peripheral neuropathy, alopecia, and hypothyroidism that is controlled with hormone replacement therapy).
  • Active, known, or suspected autoimmune disease.
    • Note: Patients with type I diabetes mellitus, hypothyroidism, adrenal or pituitary insufficiency that is controlled with hormone replacement therapy, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • History of other cancer within 2 years with the exception of basal or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the breast, cervix, prostate, or other neoplasm that has undergone potentially curative therapy with no evidence of disease recurrence following agreement with Sponsor.
  • Any severe concurrent non-cancer disease (including active systemic infection and/or uncontrolled hypertension) that, in the judgment of the Investigator, would make the patient inappropriate for the current study.
  • Active tuberculosis or recent (< 2 week) clinically significant infection, or evidence of active hepatitis B or hepatitis C.
  • Known history of positive test for human immunodeficiency (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • History of pneumonitis requiring systemic steroids for treatment (with the exception of prior resolved in-field radiation pneumonitis).
  • Patient with known central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Myocardial infarction within 6 months of study initiation, active cardiac ischemia, myocarditis, or New York Heart Association (NYHA) Grade III or IV heart failure.
  • Pregnant, planning to become pregnant, or nursing.
  • Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study.

Exclusion Criteria - Study Treatment Stage:

  • Immunosuppression from:
  • Concurrent, recent (≤ 4 weeks) or anticipated treatment with systemic corticosteroids (> 10 mg daily prednisone equivalent), or other immunosuppressive medications such as OKT3, ATG/ALG, methotrexate, tacrolimus, cyclosporine, azathioprine or rapamycin. Inhaled or topical steroids, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, steroid pre-treatment for chemotherapy (e.g., pemetrexed), antihistamines, non-steroidal anti-inflammatory drugs, and aspirin are permitted in the absence of active autoimmune disease.
  • Conditions such as common variable hypogammaglobulinemia or exposures such as large field radiotherapy.
  • Patients who have had history of life-threatening treatment-related AEs with prior immunotherapy or who have not recovered from prior cancer therapy-induced AEs (i.e., any AE that remains ≥ Grade 3, or that has not returned to baseline with the exception of alopecia, neuropathy, and hypothyroidism if controlled by hormone replacement).
    • Note: Only applicable to those AEs not covered by other inclusion and exclusion criteria (e.g., ANC values, ALT values, etc.).
  • Active, known, or suspected autoimmune disease.
    • Note: Patients with type I diabetes mellitus, hypothyroidism if requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Received radiation therapy within 2 weeks prior to first dose of study treatment.
  • Any severe concurrent non-cancer disease (including active infection and/or uncontrolled hypertension) that, in the judgment of the Investigator, would make the patient inappropriate for the current study (note: study treatment may be delayed until patient has recovered from disease [such as an infection] or has stabilized).
  • Active tuberculosis or recent (< 2 week) clinically significant infection, or evidence of active hepatitis B or hepatitis C. 
  • History of pneumonitis requiring systemic steroids for treatment (with the exception of prior resolved in-field radiation pneumonitis).
  • Patient with uncontrolled CNS metastases or brain stem metastasis, patient receiving steroids for CNS disease, and/or carcinomatous meningitis; patients with irradiated CNS metastases should be discussed on a case-by-case with the Sponsor prior to enrollment.
  • Myocardial infarction, active cardiac ischemia, myocarditis, or NYHA Grade III or IV heart failure since inclusion in the study.
  • Pregnant, planning to become pregnant, or nursing.
  • Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment that may interfere with Study Treatment per Investigator discretion.
  • Medical, psychiatric, cognitive or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the study protocol or to complete the study.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Daniel Ahn, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Kabir Mody, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions