Pan-tumor Neoadjuvant Basket Study of Immune Check-point Inhibition and Novel Immuno-oncology Combinations (NEOASIS)

  • STATUS
    Recruiting
  • End date
    Jan 29, 2034
  • participants needed
    92
  • sponsor
    The Netherlands Cancer Institute
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Updated on 29 February 2024
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Summary

In this study, the efficacy of botensilimab and balstilimab in mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors will be assessed.

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.

Details
Condition Resectable MMR-proficient Solid Tumors
Age 18 years and older
Treatment botensilimab, balstilimab
Clinical Study IdentifierNCT06279131
SponsorThe Netherlands Cancer Institute
Last Modified on29 February 2024

Eligibility

 Yes No Not Sure

Inclusion Criteria

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
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
upper limit of normal (ULN) (except for subjects with Gilbert syndrome, who
can have total bilirubin transaminases (ASAT/ALAT)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

Exclusion Criteria

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 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
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