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Trial Title:
Pan-tumor Neoadjuvant Basket Study of Immune Check-point Inhibition and Novel Immuno-oncology Combinations
NCT ID:
NCT06279130
Condition:
Resectable MMR-deficient Solid Tumors
Resectable MMR-proficient Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Basket, open-label
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
botensilimab
Description:
Anti cytotoxic T-lymphocyte associated protein-4 (anti-CTLA4)
Arm group label:
dMMR "other cancers" baskets
Arm group label:
dMMR Colorectal basket
Arm group label:
dMMR Gynaecological oncology basket
Arm group label:
dMMR Safety run-in 1
Arm group label:
dMMR Safety run-in 2
Arm group label:
dMMR Upper gastro-intestinal cancer basket
Arm group label:
pMMR Safety run-in 1
Arm group label:
pMMR Safety run-in 2
Intervention type:
Drug
Intervention name:
balstilimab
Description:
Anti programmed cell death protein-1 (anti-PD1)
Arm group label:
dMMR "other cancers" baskets
Arm group label:
dMMR Colorectal basket
Arm group label:
dMMR Gynaecological oncology basket
Arm group label:
dMMR Safety run-in 1
Arm group label:
dMMR Safety run-in 2
Arm group label:
dMMR Upper gastro-intestinal cancer basket
Arm group label:
pMMR Safety run-in 1
Arm group label:
pMMR Safety run-in 2
Summary:
In this study, the efficacy of botensilimab and balstilimab in mismatch repair deficient
(dMMR) and mismatch repair proficient (pMMR) tumors will be assessed.
Detailed description:
The NEOASIS study is an adaptive, pan-cancer, single-center, open-label, basket study
assessing the efficacy of botensilimab and balstilimab in patients with resectable dMMR
and pMMR solid tumors of various origins. Patients will be included in baskets according
to tumor type and mismatch repair (MMR) status and will receive 2 cycles of immunotherapy
followed by surgery.
The trial will commence with two safety run-in cohorts: one for patients with dMMR tumors
and one for patients with pMMR tumors that will run in parallel. These safety run-in
cohort will be used to assess safety and feasibility of pre-operative botensilimab +
balstilimab. Data from the safety run-in cohorts will be used to determine the dosing and
scheduling to be used in the MMR-specific cohorts of the main study. Safety will be
assessed according to dose limiting toxicities. In the run-in cohorts, the first five
patients will receive botensilimab 25mg intravenously (IV) on Day1 plus balstilimab 450mg
IV on Day1 and Day22. Patients 6-10 will receive botensilimab 50mg IV on Day1 plus
balstilimab 450mg IV on Day1 and Day22 followed by surgery 8 weeks after registration.
After full accrual of the run-in cohorts, MMR-specific baskets including a "other
cancers" basket will start accrual with the optimal dose and schedule as determined in
the safety run-in followed by surgery 8 weeks after registration. The MMR-specific
baskets are designed with a Simon's 2 stage design in which first 8 patients will be
included, if in the first 8 patients >2 Major pathological responses are reported
(defined as ≤10% residual viable tumor) accrual of 10 more patients will continue for a
total of 18 patients per basket.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed written informed consent
2. Patients at least 18 years of age
3. Non-metastatic, newly diagnosed dMMR and pMMR cancers either fitting within a
specific basket or in the "other" cohort (e.g. sarcoma, head and neck cancers, anal
cancer, esophageal SCC)
4. In case of pMMR tumors: no indication for neoadjuvant therapy according to standard
of care, unless adjuvant treatment is considered a standard of care alternative;
5. Eligible for study biopsy
6. World health organization (WHO) performance status of 0 or 1
7. Screening laboratory tests must meet the following criteria and should be obtained
within 7 days prior to randomization/registration: White blood cell count (WBC > 2.0
x 10^9/L, Absolute neutrophil count (ANC) > 1.5x10^9/L, platelets > 100 x 10^9/L,
Hemoglobin > 5.0mmol/L. Transfusion is allowed to obtain an adequate hemoglobin
level. Liver function tests: total bilirubin < 1.5 upper limit of normal (ULN)
(except for subjects with Gilbert syndrome, who can have total bilirubin <3.0
mg/dL); alkaline phosphatase <1.5 ULN; transaminases (ASAT/ALAT) <3 x ULN; Lactate
dehydrogenase (LDH) < 1.5x ULN; Creatinine clearance (Cockcroft-Gault) of >45
ml/min, Albumin > 3.0 g/dL
8. Women of childbearing potential (WOCBP)* must use appropriate method(s) of
contraception. WOCBP should use an adequate method to avoid pregnancy for 20 weeks
after the last dose of investigational drug, Non-childbearing potential is defined
as:
1. Postmenopausal: ≥ 50 years of age and has not had menses for greater than 1
year.
2. Amenorrheic for ≥ 2 years without a hysterectomy and bilateral oophorectomy and
a follicle- stimulating hormone value in the postmenopausal range upon
pre-study(screening) evaluation.
3. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation.
9. Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
the start of cycle 1 day 1
10. Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year. Men receiving the study treatment and who are
sexually active with WOCBP (excluding azoospermic men) will be instructed to adhere
to contraception for a period of 28 weeks after the last dose of investigational
drug and are not allowed to donate sperm during that timeframe.
Exclusion Criteria:
1. Signs of distant metastases on imaging and physical examination
2. Clinical obstruction
3. Clinical symptoms or radiological suspicion of perforation
4. Previous treatment with immune checkpoint inhibitors including but not limited to
anti-CTLA4 or anti-PD1
5. Prior chemotherapy for any cancer
6. Radiotherapy prior to or planned post-surgery radiotherapy for disease under study
7. Active malignancies other than disease under study within 3 years prior to
inclusion, except for malignancies with a negligible recurrence rate (e.g. <10% in 5
years)
8. Allergies and Adverse Drug Reaction:
1. History of allergy to study drug components
2. History of severe hypersensitivity reaction to any monoclonal antibody
9. Intercurrent illnesses, including but not limited to infections, unstable angina
pectoris
10. Underlying medical conditions that, in the investigator's opinion, will make the
administration of the study drug hazardous or obscure the interpretation of toxicity
determination of adverse events
11. Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus
ribonucleic acid (HCV antibody) indicating acute or chronic infection
12. History of testing positive for human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS)
13. Active autoimmune disease or a documented history of autoimmune disease, or other
medical conditions requiring systemic steroid or immunosuppressive medications,
except for subjects with vitiligo, diabetes mellitus type 1, hypothyroidism due to
autoimmune condition only requiring hormone replacement, psoriasis or resolved
childhood asthma/atopy not requiring systemic treatment
14. Conditions 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
15. Live vaccines in the 4 weeks prior to inclusion
16. Psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule
17. Current pregnancy or breastfeeding
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Netherlands Cancer Institute
Address:
City:
Amsterdam
Zip:
1066 CX
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Marieke van de Belt, MsC
Investigator:
Last name:
Myriam Chalabi, MD PhD
Email:
Principal Investigator
Start date:
January 29, 2024
Completion date:
January 29, 2034
Lead sponsor:
Agency:
The Netherlands Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Agenus Inc.
Agency class:
Industry
Source:
The Netherlands Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06279130
