Trial Title:
Combined AlloStim+Anti-PD-L1 in 4L MSS Metastatic Colorectal Cancer
NCT ID:
NCT06557278
Condition:
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Avelumab
Conditions: Keywords:
colorectal cancer
checkpoint inhibitor
AlloStim
immunotherapy
avelumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
AlloStim
Description:
experimental immunotherapy to prime for checkpoint inhibitor
Intervention type:
Drug
Intervention name:
Bavencio
Description:
anti-PDL1 checkpoint inhibitor
Other name:
Avelumab
Summary:
Experimental immunotherapy in chemotherapy-refractory and immunotherapy-refractory
metastatic colorectal cancer patients that have progressed, or are intolerant to,
Longsurf (TAS-102) +/- Avastin (bevacizumab) or Stivarga (regorafenib) or Fruzaqla
(fruquintinib) combining experimental AlloStim with an anti-programmed death ligand 1
(PD-L1) checkpoint inhibitor drug.
Detailed description:
The protocol provides fourth-line experimental treatment for subjects with microsatellite
stable (MSS)/ proficient mismatch repair (pMMR) metastatic colorectal cancer. These
patients do not respond to checkpoint inhibitors. This study will investigate whether
AlloStim® administered weekly in two-21 day cycles with each cycle consisting of 3 weekly
intradermal (ID) doses followed the last week with an intravenous (IV) dose (3 cycles
=Days 0 through 49) can prime patients to become responsive to checkpoint inhibition
immunotherapy. A restaging computed tomography (CT) scan is conducted on day 56 after the
priming and will be compared to the baseline CT scan by Response Evaluation Criteria in
Solid Tumors (RECIST 1.1). Scans at day 56 are expected to be read as radiological
progression upon restaging after AlloStim® priming, possibly due to immunological
swelling, known as "pseudoprogression", consistent with the presumed inflammatory
mechanism of action of AlloStim®. This mechanism may convert "cold" tumors to "hot"
tumors. The immune cell infiltrates of tumors after AlloStim® include T-helper cell type
1 (Th1) memory cells which produce interferon-gamma. Interferon-gamma is known to
increase expression of anti-programmed death ligand 1 (PD-L1) checkpoint molecules in the
tumor microenvironment. Higher PD-L1 expression may convert checkpoint inhibitor
unresponsive tumors to become checkpoint inhibitor responsive. After two 21-day cycles of
AlloStim® priming, a combination of AlloStim® IV boosters and anti-PD-L1 checkpoint
therapy (with avelumab 800 mg q/2 weeks) is scheduled between days 63 to day 98, A
restaging CT scan at day 112 is then compared to day 56 and baseline to determine if the
tumor target lesions' size has changed. An expansion phase providing another cycle of
combined AlloStim® and avelumab is provided for stable patients from days 119-154. A
final restaging CT scan is conducted on Day 168 for all subjects.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adult male and female subjects aged 18-80 years at screening visit
2. Pathologically confirmed diagnosis of MSS/pMMR colorectal adenocarcinoma
3. Presenting with metastatic disease:
- Primary tumor can be intact or previously resected
4. Previous treatment failure of at least two lines of active systemic chemotherapy:
- Previous chemotherapy must have included a fluoropyrimidine, oxaliplatin (e.g.
FOLFOX, CAPOX), and irinotecan-containing (e.g. FOLFIRI) regimens (single
regimen of FOLFIRINOX satisfies)
- Administered in adjuvant setting or for treatment of metastatic disease
- If KRAS wild type, must have at least one prior anti-EGFR therapy if left sided
primary tumor
5. Treatment failure or refusal/not qualified for at least one third-line treatment
- TAS-102 +/- bevacizumab or regorafenib or fruquinib
- Treatment failure can be due to disease progression or toxicity
- Time from last treatment failure to Informed Consent must be no more than 30
days
6. ECOG performance score: 0-1
7. Adequate hematological function:
- Absolute granulocyte count ≥ 1,200/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9.0 g/dL (may be corrected by transfusion)
8. Adequate Organ Function:
- Creatinine ≤ 1.5 mg/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
9. Alkaline phosphatase ≤ 2.5 times ULN *
10. Aspartate aminotransferase (AST) or (SGOT) ≤ 2.5 times ULN *
11. Alanine aminotransferase (ALT) or (SGPT) ≤ 2.5 times ULN*
12. EKG without clinically relevant abnormalities
13. Female subjects: Not pregnant or lactating
14. Patients with childbearing potential must have a negative ß-HCG test and agree to
use a highly effective contraceptive method during the course of the study
15. Study specific Informed Consent in the native language of the subject
- ≤ 5 times ULN if liver involvement
Exclusion Criteria:
1. High frequency microsatellite instability (MSI-H) or deficient mismatched repair
dMMR
2. Bowel obstruction or high risk for obstruction if tumors become inflamed
3. Moderate or severe ascites requiring medical intervention
4. Clinical evidence of brain metastasis or leptomeningeal involvement
5. Widespread peritoneal carcinomatous (e.g. CT scan shows innumerable lesions visible
and/or abnormal thickening of greater omentum) that increases risk of a major
morbidity (e.g. bowel obstruction) in the opinion of the Investigator
6. COPD
7. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in
pulmonary dysfunction requiring active treatment; or, oxygen saturation <92% on room
air
8. Any of the following mood disorders: active major depressive episode, recent history
of suicidal attempt or ideation
9. Prior allogeneic bone marrow/stem cell or solid organ transplant
10. Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent
(dose equivalent to > 5 mg/day of prednisone) planned or anticipated during the
study before the end of the Safety Evaluation Period (28 days after the last dose of
IP)
- Topical corticosteroids are permitted
11. Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis,
multiple sclerosis, autoimmune thyroid disease, uveitis)
- Well controlled Type I diabetes allowed (HbA1c < 8.5%)
12. Prior experimental immunotherapy
13. History of blood transfusion reactions
14. Progressive viral or bacterial infection
o All infections must be resolved and the subject must remain afebrile for seven
days without antibiotics prior to being placed on study
15. Cardiac disease of symptomatic nature
16. History of HIV positivity or AIDS
17. History of severe hypersensitivity to monoclonal antibody drugs
18. Psychiatric or addictive disorders or other condition that, in the opinion of the
Investigator, would preclude study participation.
19. Subjects that lack ability to provide consent for themselves
20. Any prior cancer diagnosis (other than cured basal cell carcinoma, head and neck
carcinoma in-situ, superficial Ta, Tis, T1 bladder cancer, or papillary carcinoma of
thyroid) or concurrent cancer histologically different than colorectal
adenocarcinoma
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Mt. Sinai Comprehensive Cancer Center
Address:
City:
Miami Beach
Zip:
33140
Country:
United States
Facility:
Name:
Hirschfield Oncology Center
Address:
City:
Brooklyn
Zip:
11206
Country:
United States
Contact:
Last name:
Karla Witkowski
Phone:
718-732-4050
Email:
karla@honcology.com
Investigator:
Last name:
Azriel Hirschfeld, MD
Email:
Principal Investigator
Facility:
Name:
New York Cancer and Blood Specialists
Address:
City:
Shirley
Zip:
11967
Country:
United States
Contact:
Last name:
Ivanna Novoa, CRC
Phone:
631-675-5075
Email:
inova@nycancer.com
Contact backup:
Last name:
Carmen Vicuna, CRC
Email:
cvicuna@nycancer.com
Investigator:
Last name:
Richard Zuniga, MD
Email:
Principal Investigator
Investigator:
Last name:
Gurmohan Syali, MD
Email:
Sub-Investigator
Investigator:
Last name:
Samir Patel, MD
Email:
Sub-Investigator
Investigator:
Last name:
Sanjeev Jain, MD
Email:
Sub-Investigator
Investigator:
Last name:
David Eagle, MD
Email:
Sub-Investigator
Investigator:
Last name:
Amishi Desai, MD
Email:
Sub-Investigator
Investigator:
Last name:
Roy Chen, MD
Email:
Sub-Investigator
Investigator:
Last name:
Alfredo Torres, MD
Email:
Sub-Investigator
Investigator:
Last name:
Noshir Dacosta, MD
Email:
Sub-Investigator
Investigator:
Last name:
Yelda Nouri, MD
Email:
Sub-Investigator
Investigator:
Last name:
Regina Jablonski, MD
Email:
Sub-Investigator
Investigator:
Last name:
Shahid Nawaz, MD
Email:
Sub-Investigator
Investigator:
Last name:
David Chu, MD
Email:
Sub-Investigator
Investigator:
Last name:
Jerry George, DO
Email:
Sub-Investigator
Investigator:
Last name:
Steven Montana, DO
Email:
Sub-Investigator
Investigator:
Last name:
Harry Staszewski, MD
Email:
Sub-Investigator
Start date:
November 2024
Completion date:
November 2025
Lead sponsor:
Agency:
Mirror Biologics, Inc.
Agency class:
Industry
Source:
Mirror Biologics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06557278
https://rdcu.be/dHXGN
