Trial Title:
A Study of Botensilimab (AGEN1181) for the Treatment of Advanced Melanoma
NCT ID:
NCT05529316
Condition:
Advanced Melanoma
Conditions: Official terms:
Melanoma
Conditions: Keywords:
Open-label
Monotherapy
Combination Therapy
Anti-PD-1
Anti-PD-L1
Anti-CTLA-4
Immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Suspended
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Botensilimab
Description:
An anti-CTLA-4 monoclonal antibody
Arm group label:
Part 1 Cohort A: Botensilimab
Arm group label:
Part 1 Cohort B: Botensilimab
Arm group label:
Part 2 Cohort A: Botensilimab + Balstilimab
Arm group label:
Part 2 Cohort B: Botensilimab + Balstilimab
Other name:
AGEN1181
Intervention type:
Drug
Intervention name:
Balstilimab
Description:
An anti-PD-1 monoclonal antibody
Arm group label:
Part 2 Cohort A: Botensilimab + Balstilimab
Arm group label:
Part 2 Cohort B: Botensilimab + Balstilimab
Other name:
AGEN2034
Summary:
This study is an open-label, 2-part, Phase 2, multicenter study to evaluate the efficacy,
safety, tolerability, and pharmacokinetic profiles of botensilimab as monotherapy and in
combination with balstilimab in participants with advanced cutaneous melanoma refractory
to checkpoint inhibitor therapy.
Detailed description:
This Phase 2 study will enroll up to approximately 220 evaluable adult participants with
a histologically confirmed diagnosis of either Stage III (unresectable) or Stage IV
cutaneous melanoma and who have had prior treatments with anti-programmed death (ligand)
1 [PD-(L)1].
This study will consist of 2 parts. Part 1 consists of 2 cohorts (Cohorts A and B) that
will receive botensilimab monotherapy. In Cohort A, participants refractory to PD-(L)1
will receive botensilimab. In Cohort B, participants refractory to PD-(L)1 and cytotoxic
T-lymphocyte antigen 4 (CTLA-4) will receive botensilimab. Part 2 consists of Cohorts A
and B that will receive botensilimab combination therapy. In Cohort A, participants
refractory to PD-(L)1 will receive botensilimab in combination with balstilimab. In
Cohort B, participants refractory to PD-(L)1 and CTLA-4 will receive botensilimab in
combination with balstilimab.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
To participate in the study, participants must meet all the following inclusion criteria:
Cohort A only:
1. Prior treatment with anti-PD-(L)1 therapy (for example, pembrolizumab or nivolumab)
for at least 6 weeks and radiologic progression confirmed by 2 scans at least 4
weeks apart, or if symptomatic due to progressive malignancy, then 1 scan showing
progression is sufficient.
2. Progression must be either on treatment with anti-PD-(L)1 regimen or ≤ 12 weeks from
last anti-PD-(L)1 dose in metastatic setting or ≤ 24 weeks from completion of
therapy in adjuvant/ neoadjuvant setting.
3. For Part 2 only, no intervening anti-cancer therapy between the last course of
anti-PD-(L)1 treatment and the first dose of study treatment except for local
measures (for example, surgical excision, biopsy, focal radiation therapy), or BRAF
± MEK inhibition when applicable in BRAF mutant participants.
Cohort B only:
1. Prior treatment with first-generation anti-CTLA-4 therapy (for example, ipilimumab
or tremelimumab) and prior treatment with anti-PD-(L)1 for at least 6 weeks.
2. Progression on most recent anti-neoplastic therapy.
3. For Part 2 only, no more than 3 prior lines of therapy in the advanced setting for
BRAF mutant and no more than 2 prior lines of therapy in the advanced setting in the
BRAF wild type.
Cohorts A and B:
1. Voluntarily agree to participate by giving signed, dated, and written informed
consent prior to any study-specific procedures.
2. Histological confirmation of Stage III (unresectable) or Stage IV cutaneous
melanoma, per the American Joint Committee on Cancer 8th edition staging system.
3. Measurable disease on baseline imaging per RECIST 1.1 criteria.
4. BRAF V600 mutation status or consent to BRAF V600 mutation testing per local
institutional standards during the screening period.
5. Life expectancy ≥ 3 months.
6. Eastern Cooperative Oncology Group performance status of 0 or 1.
7. Adequate organ function is defined as the following laboratory values within 21 days
of Cycle 1 Day 1 (C1D1):
1. Neutrophils > 1500/microliter (μL) (stable off any growth factor within 4 weeks
of first study treatment administration).
2. Platelets > 100 × 10^3/μL (transfusion to achieve this level is not permitted
within 2 weeks of first study treatment administration).
3. Hemoglobin > 8.0 grams/deciliter (g/dL) (transfusion to achieve this level is
not permitted within 2 weeks of first study treatment administration).
4. Creatinine clearance ≥ 45 milliliters/minute (measured or calculated using
modification of diet in renal disease).
5. Aspartate aminotransferase/alanine aminotransferase < 3.0 × upper limit of
normal (ULN).
6. Total bilirubin < 1.5 × ULN, or < 3.0 × ULN for participants with Gilbert
syndrome.
7. Albumin ≥ 3.0 g/dL.
8. International normalized ratio or prothrombin time ≤ 1.5 × ULN and activated
partial thromboplastin time ≤ 1.5 × ULN (unless participant is receiving
anticoagulant therapy).
8. Participant must provide a formalin-fixed paraffin-embedded tumor tissue sample from
the most recent biopsy of a tumor lesion, obtained within 90 days from signing
informed consent form. If recent tumor tissue is unavailable or inadequate, a fresh
biopsy will be required, unless the Sponsor agrees that it is not safe/feasible.
9. Women of childbearing potential (WOCBP) must have a negative urine or serum
pregnancy test at screening (within 72 hours of first dose of study medication) and
prior to study drug administration. In part 1, WOCBP must agree to use highly
effective contraceptive measures starting with the screening visit through 3 months
after the last dose of study treatment. In Part 2, WOCBP must agree to use highly
effective contraceptive measures starting with the screening visit through 5 months
after the last dose of study treatment. Note: Abstinence is acceptable if this is
the established and preferred contraception for the participant.
10. In Part 1, male participants with a female partner(s) of childbearing potential must
agree to use highly effective contraceptive measures throughout the study, starting
with the screening visit through 3 months after the last dose of study treatment is
received. In Part 2, male participants with a female partner(s) of childbearing
potential must agree to use highly effective contraceptive measures throughout the
study starting with the screening visit through 5 months after the last dose of
study treatment is received. Males with pregnant partners must agree to use a
condom; no additional method of contraception is required for the pregnant partner.
Exclusion Criteria:
To participate in the study, participants must meet none of the following exclusion
criteria:
Cohort A:
1. Received prior anti-CTLA-4 therapy.
Cohort B:
1. Received prior Fc-engineered or Fc-enhanced anti-CTLA-4 therapy (for example,
BMS-96218, BMS-986288, HBM4003, XTX101, CTLA-4 targeting bispecific or other
approaches such as ONC-392).
Cohorts A and B:
1. Ocular, uveal, or mucosal melanoma.
2. Any persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE]
Grade ≥ 2) from prior cancer therapy, excluding endocrinopathies stable on
medication, stable neuropathy, and alopecia.
3. Any history of CTCAE Grade ≥ 3 immune-mediated toxicity (excluding endocrinopathies
and non-necrotizing/bullous rash) from prior checkpoint inhibition.
4. Refractory ascites require 2 or more therapeutic paracentesis in the last 4 weeks or
≥ 4 within the last 90 days prior to study entry.
5. Bowel obstruction within the past 3 months or an impending bowel obstruction.
6. Clinically significant (that is, active) cardiovascular disease: cerebral vascular
accident/stroke or myocardial infarction within 6 months of enrollment, unstable
angina, congestive heart failure (New York Heart Association class ≥ III), or
serious uncontrolled cardiac arrhythmia requiring medication.
7. Active brain metastases or leptomeningeal metastases with the following exceptions:
1. Treated brain metastases require a) surgical resection, or b) stereotactic
radiosurgery. These participants must be off steroids ≥ 10 days prior to
randomization for the purpose of managing their brain metastases. Repeat brain
imaging following surgical resection or stereotactic radiosurgery is not
required if their last brain magnetic resonance imaging is within screening
window. Whole-brain radiation is not allowed.
2. Untreated isolated brain metastases that are too small for treatment by
surgical resection or stereotactic radiosurgery (for example, 1-2 millimeters)
and/or of uncertain etiology are potentially eligible but need to be discussed
with and approved by the study Medical Monitor.
8. Concurrent malignancy (present during screening) requiring treatment or history of
prior malignancy active within 2 years prior to the first dose of study treatment
(that is, participants with a history of prior malignancy are eligible if treatment
was completed at least 2 years before the first dose of study treatment and the
participant has no evidence of disease). Participants with history of prior
early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for
active surveillance or noninvasive or in situ cancers who have undergone definitive
treatment at any time are also eligible.
9. Incomplete resolution of clinically significant adverse events related to most
recent therapy/intervention prior to enrollment.
10. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine or booster < 7
days before C1D1. For vaccines requiring more than 1 dose, the full series should be
completed prior to C1D1, when feasible. A booster shot is not required but also must
be administered > 7 days from C1D1 or > 7 days from future cycle on study.
11. Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
12. Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior
history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
13. History of allogeneic organ transplant.
14. Psychiatric or substance abuse disorders that would interfere with cooperation with
the requirements of the study.
15. Participants with a condition requiring systemic treatment with either
corticosteroids (> 10 milligrams [mg] daily prednisone equivalent) within 14 days or
another immunosuppressive medication within 30 days of the first dose of study
treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10
mg daily prednisone equivalent, are permitted in the absence of active autoimmune
disease.
16. Active autoimmune disease or history of autoimmune disease that required systemic
treatment within 2 years before starting study treatment (that is, with use of
disease-modifying agents or immunosuppressive drugs).
17. History or current evidence of any condition, co-morbidity, therapy, any active
infections, or laboratory abnormality that might confound the results of the study,
interfere with the participants participation for the full duration of the study, or
is not in the best interest of the participant to participate, in the opinion of the
treating Investigator.
18. A WOCBP who is pregnant or breastfeeding or WOCBP who are not willing to employ
effective birth control from screening to 90 days after the last dose of
botensilimab (whichever is later).
19. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or
20 days for severe/critical illness prior to C1D1.
20. Uncontrolled infection with human immunodeficiency virus (HIV). Participants on
stable highly active antiretroviral therapy with undetectable viral load and normal
cluster of differentiation 4 counts for at least 6 months prior to study entry are
eligible. Serological testing for HIV at screening is not required.
21. Known to be positive for hepatitis B virus (HBV) surface antigen, or any other
positive test for HBV indicating acute or chronic infection. Participants who are
receiving or who have received anti-HBV therapy and have undetectable HBV DNA for at
least 6 months prior to study entry are eligible. Serological testing for HBV at
screening is not required.
22. Known active hepatitis C virus (HCV) as determined by positive serology and
confirmed by polymerase chain reaction (PCR). Participants on or who have received
antiretroviral therapy are eligible, provided they are virus-free by PCR for at
least 6 months prior to study entry. Serological testing for HCV at screening is not
required.
23. Dependence on total parenteral nutrition.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Scottsdale Healthcare Hospitals DBA HonorHealth
Address:
City:
Scottsdale
Zip:
85258
Country:
United States
Facility:
Name:
Virginia K. Crosson Cancer Center at St. Jude Medical Center
Address:
City:
Fullerton
Zip:
92835
Country:
United States
Facility:
Name:
Providence Saint John's Health Center
Address:
City:
Santa Monica
Zip:
90404
Country:
United States
Facility:
Name:
Yale University School of Medicine - Yale Cancer Center
Address:
City:
New Haven
Zip:
06520-8028
Country:
United States
Facility:
Name:
Georgetown University Medical Center
Address:
City:
Washington
Zip:
20057
Country:
United States
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
John Theurer Cancer Center at Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Facility:
Name:
Universitair Ziekenhuis Brussel
Address:
City:
Jette
Zip:
1090
Country:
Belgium
Facility:
Name:
Oncosite - Centro de Pesquisa Clinica Em Oncologia
Address:
City:
Ijuí
Zip:
98700-000
Country:
Brazil
Facility:
Name:
Centro de Pesquisas Clinicas da Fundação Doutor Amaral Carvalho
Address:
City:
Jaú
Zip:
17210-080
Country:
Brazil
Facility:
Name:
Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa
Address:
City:
Porto Alegre
Zip:
90110-270
Country:
Brazil
Facility:
Name:
INCA II - Instituto Nacional de Cancer Jose Alencar Gomes da Silva
Address:
City:
Rio de Janeiro
Zip:
20220-410
Country:
Brazil
Facility:
Name:
Hospital Sirio Libanes
Address:
City:
São Paulo
Zip:
01308-050
Country:
Brazil
Facility:
Name:
Real e Benemerita Associaçao Portuguesa de Beneficencia - A Beneficencia Portuguesa de Sao Paulo
Address:
City:
São Paulo
Zip:
01323-001
Country:
Brazil
Facility:
Name:
Hospital A.C. Camargo Cancer Center
Address:
City:
São Paulo
Zip:
01509-010
Country:
Brazil
Facility:
Name:
CHU Amiens Picardie - Hopital Sud
Address:
City:
Amiens
Zip:
80054
Country:
France
Facility:
Name:
CHU Grenoble-Alpes - Hopital Michallon
Address:
City:
La Tronche
Zip:
38700
Country:
France
Facility:
Name:
Centre Leon Berard
Address:
City:
Lyon
Zip:
69008
Country:
France
Facility:
Name:
CHU de Nantes
Address:
City:
Nantes Cedex 1
Zip:
44093
Country:
France
Facility:
Name:
AP-HP Hopital Saint-Louis
Address:
City:
Paris
Zip:
75010
Country:
France
Facility:
Name:
Centre Eugene Marquis
Address:
City:
Rennes
Zip:
35042
Country:
France
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Country:
France
Facility:
Name:
Universitaetsklinikum Essen
Address:
City:
Essen
Zip:
45122
Country:
Germany
Facility:
Name:
Universitaetsklinikum Hamburg-Eppendorf
Address:
City:
Hamburg
Zip:
20246
Country:
Germany
Facility:
Name:
Universitaetsklinikum Heidelberg
Address:
City:
Heidelberg
Zip:
69120
Country:
Germany
Facility:
Name:
University Hospital Schleswig-Holstein
Address:
City:
Kiel
Zip:
24105
Country:
Germany
Facility:
Name:
Universitaetsmedizin der Johannes Gutenberg - Universitaet Mainz
Address:
City:
Mainz
Zip:
55131
Country:
Germany
Facility:
Name:
Klinikum der Universitaet München
Address:
City:
Munchen
Zip:
80377
Country:
Germany
Facility:
Name:
Universitaetsklinikum Tuebingen
Address:
City:
Tuebingen
Zip:
72076
Country:
Germany
Facility:
Name:
Universitaetsklinikum Würzburg
Address:
City:
Würzburg
Zip:
97080
Country:
Germany
Facility:
Name:
IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l.
Address:
City:
Meldola
Zip:
47014
Country:
Italy
Facility:
Name:
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Facility:
Name:
Azienda Ospedaliero Universitaria Senese
Address:
City:
Siena
Zip:
53100
Country:
Italy
Facility:
Name:
Branch Office of "Hadassah Medical Ltd"
Address:
City:
Moscow
Zip:
121205
Country:
Russian Federation
Facility:
Name:
LLC Medical Services
Address:
City:
Saint Petersburg
Zip:
194356
Country:
Russian Federation
Facility:
Name:
Clinical Hospital Russian Railways - Medicine
Address:
City:
Saint Petersburg
Zip:
195271
Country:
Russian Federation
Facility:
Name:
Petrov National Medical Research Center of Oncology
Address:
City:
Saint Petersburg
Zip:
197758
Country:
Russian Federation
Facility:
Name:
Hospital Universitario Vall d'Hebron
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Facility:
Name:
Hospital Clinic Barcelona
Address:
City:
Barcelona
Zip:
8036
Country:
Spain
Facility:
Name:
Onkologikoa
Address:
City:
Donostia
Zip:
20014
Country:
Spain
Facility:
Name:
Hospital General Universitario Gregorio Maranon
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen Macarena
Address:
City:
Sevilla
Zip:
41009
Country:
Spain
Facility:
Name:
Consorcio Hospital General Universitario de Valencia
Address:
City:
Valencia
Zip:
46014
Country:
Spain
Facility:
Name:
CHUV - Centre hospitalier universitaire vaudois
Address:
City:
Lausanne
Zip:
1011
Country:
Switzerland
Facility:
Name:
Universitaetsspital Zuerich
Address:
City:
Zuerich
Zip:
CH-8091
Country:
Switzerland
Facility:
Name:
Royal Marsden Foundation Trust
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Facility:
Name:
Mount Vernon Cancer Centre
Address:
City:
Middlesex
Zip:
HA6 2RN
Country:
United Kingdom
Start date:
December 12, 2022
Completion date:
May 2028
Lead sponsor:
Agency:
Agenus Inc.
Agency class:
Industry
Source:
Agenus Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05529316
