A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy in Patients With Operable Melanoma

Phase II Randomized Study of Neoadjuvant Pembrolizumab Alone or in Combination With CMP-001 in Patients With Operable Melanoma: Efficacy and Biomarker Study

Sponsors

Commanditaire principal: National Cancer Institute (NCI)

La source National Cancer Institute (NCI)
Bref résumé

This phase II trial studies the effect of pembrolizumab alone or in combination with CMP-001 in treating patients with melanoma that can be treated by surgery (operable). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with CMP-001 may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. The addition of CMP-001 to pembrolizumab could improve the ability of the immune system to shrink tumors and to prevent them from returning.

Description détaillée

PRIMARY OBJECTIVE: I. To evaluate the rate of pathologic complete response (pCR) rate in each arm. SECONDARY OBJECTIVES: I. To evaluate the rate of pathologic near-complete/major response (pMR) of the neoadjuvant therapy in each arm. II. To evaluate the pathologic response rate of un-injected lesions on the combination arm. III. To evaluate relapse-free survival (RFS) in each arm. IV. To evaluate overall survival (OS) in each arm. V. To evaluate the preoperative radiographic response rate in each arm. VI. To evaluate safety and toxicity of neoadjuvant therapy in each arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: NEOADJUVANT PHASE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. ARM B: NEOADJUVANT PHASE: Patients receive VLP-encapsulated TLR9 agonist CMP-001 (CMP-001) subcutaneously (SC) on day 1 of cycle 1 and then intratumorally on days 8 and 15 of cycle 1, days 1, 8, and 15 of cycle 2, and day 1 of cycle 3. Patients also receive pembrolizumab IV over 30 minutes on day 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months if < 2 years from study entry, every 6 months if 2-5 years from study entry, and every 12 months if > 5 years from study entry for up to 10 years (15 years total follow up).

Situation globale Not yet recruiting
Date de début March 15, 2021
Date d'achèvement November 30, 2021
Date d'achèvement principale November 30, 2021
Phase Phase 2
Type d'étude Interventional
Résultat primaire
Mesure Plage de temps
Pathologic complete response rate Up to 15 years
Résultat secondaire
Mesure Plage de temps
Radiographic response rate Up to 15 years
Relapse-free survival From randomization to relapse or death (whichever occurs first), assessed up to 15 years
Overall survival From randomization to death from any cause, assessed up to 15 years
Incidence of adverse events Up to 30 days after the last study drug administration
Inscription 54
État
Intervention

Type d'intervention: Biological

Nom de l'intervention: Pembrolizumab

La description: Given IV

Type d'intervention: Procedure

Nom de l'intervention: Surgical Procedure

La description: Undergo surgery

Type d'intervention: Drug

Nom de l'intervention: VLP-encapsulated TLR9 Agonist CMP-001

La description: Given SC or intratumorally

Étiquette du groupe d'armements: Arm B (CMP-001, pembrolizumab)

Admissibilité

Critères:

Inclusion Criteria: - Patient must be >= 18 years of age - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Patient must have a histologic diagnosis of melanoma belonging to the following American Joint Committee on Cancer (AJCC) 8th edition TNM stages: - T0, Tx or T1-4; and - N2b, N2c, N3b or N3c - Patients may have a presentation with primary melanoma with concurrent regional nodal and/or in-transit metastasis and/or distant cutaneous or nodal metastases; or patients may have a history of primary melanoma or unknown primary melanoma presenting with clinically detected regional nodal and/or in-transit recurrence; and may belong to any of the following groups: - Primary cutaneous melanoma with clinically apparent regional lymph node metastases and/or in-transit metastases - Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin - Primary cutaneous melanoma with concurrent nodal disease involving a single regional nodal group - Clinically detected nodal melanoma (if single site) arising from an unknown primary - In-transit cutaneous metastases with or without regional lymph node involvement permitted if considered potentially surgically resectable at baseline - NOTE: Patients with mucosal and/or uveal melanoma are not eligible for the study - Patient must be candidate for definitive surgery and have met with the treating surgical oncologist prior to randomization - Patient must have the presence of injectable and measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, documented by scans obtained within 4 weeks prior to randomization - NOTE: Injectable disease is defined as an accessible lesion in the skin, subcutaneous tissue or lymph nodes (LN) close to the skin and palpable by physical examination or approachable with ultrasound guidance - Absolute neutrophil count (ANC) >= 1,500 /mcL (obtained within 4 weeks prior to randomization) - Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (obtained within 4 weeks prior to randomization) - Platelets >= 100,000 / mcL (obtained within 4 weeks prior to randomization) - Serum creatinine =< 1.5 x upper limit of normal (ULN) or measured or calculated creatinine clearance > 60 mL/min (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl] for patients with creatinine levels > 1.5 x institutional ULN) (obtained within 4 weeks prior to randomization) - Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 ULN (obtained within 4 weeks prior to randomization) - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (obtained within 4 weeks prior to randomization) - International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (obtained within 4 weeks prior to randomization) - Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (obtained within 4 weeks prior to randomization) - Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial - For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated - Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load - Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial - Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better Exclusion Criteria: - Patient must not have received any live vaccine within 30 days prior to randomization. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine - Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A urine or serum pregnancy test must be repeated within 72 hours prior to receiving the first dose of pembrolizumab if the test done for eligibility/randomization is done outside of this 72 hour window. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) - Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or abstaining from sexual intercourse from time of randomization, while on study treatment, and continue for 26 weeks after the last dose of protocol treatment - Patient must not have received prior therapy with an anti-PD-1, anti-PD-L1, anti-CTLA-4, BRAF/MEK inhibitor combination and/or TLR-9 agonist - Patient must not have a diagnosis of immunodeficiency or be receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization, except as noted here - Patients who are currently receiving steroids at a dose of prednisone =< 10 mg daily (or equivalent) are permitted to enroll - Patients who require topical, ophthalmologic and inhalational steroids are permitted to enroll - Patients with hypothyroidism who are stable on hormone replacement are permitted to enroll - Patients who require active immunosuppression (greater than steroid dose discussed) for any reason are ineligible - Patients with a history of brain metastases are not eligible for this study as they do not meet the eligibility staging criteria - Patient must not have an allogeneic tissue/solid organ transplant - Patient must not have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis - Patient must not have severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients - Patient must not have an active infection requiring systemic therapy - Patient must not have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Le sexe: All

Âge minimum: 18 Years

Âge maximum: N/A

Volontaires en santé: No

Officiel général
Nom de famille Rôle Affiliation
Ahmad Tarhini Principal Investigator ECOG-ACRIN Cancer Research Group
Date de vérification

January 2021

Partie responsable

Type: Sponsor

Parcourir l'état
Nombre d'armes 2
Groupe d'armes

Étiquette: Arm A (pembrolizumab)

Type: Experimental

La description: NEOADJUVANT PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

Étiquette: Arm B (CMP-001, pembrolizumab)

Type: Experimental

La description: NEOADJUVANT PHASE: Patients receive CMP-001 SC on day 1 of cycle 1 and then intratumorally on days 8 and 15 of cycle 1, days 1, 8, and 15 of cycle 2, and day 1 of cycle 3. Patients also receive pembrolizumab IV over 30 minutes on day 8 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgery 1-2 weeks after completion of neoadjuvant phase. ADJUVANT PHASE: After recovery from surgery, patients receive pembrolizumab IV over 30 minutes on day 1 of every other cycle. Treatment repeats every 21 days for up to 16 cycles in the absence of disease progression or unacceptable toxicity.

Données patient Yes
Informations sur la conception de l'étude

Allocation: Randomized

Modèle d'intervention: Parallel Assignment

Objectif principal: Treatment

Masquage: Single (Outcomes Assessor)

Description du masquage: Pathologists

La source: ClinicalTrials.gov