AlloStim® Immunotherapy Dosing Alone or in Combination With Cryoablation in Metastatic Colorectal Cancer

NCT02380443 | Completed Phase 2 Results DMC

• 1 other identifier: ITL-019-CORK-CRYVAC
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open label dose frequency escalation study of CryoVax®. personalized anti-tumor vaccine protocol combining the cryoablation of a selected metastatic lesion with intra-lesional immunotherapy with AlloStim®. The in-situ (in the body) cancer vaccine step combines killing a single metastatic tumor lesion by use of cryoablation in order to cause the release of tumor-specific markers to the immune system and then injecting bioengineered allogeneic immune cells (AlloStim®) into the lesion as an adjuvant in order to modulate the immune response and educate the immune system to kill other tumor cells where ever they reside in the body.

Conditions

Colorectal Cancer Metastatic

Keywords

colorectal cancer; KRAS mutant; BRAF mutant; metastatic; liver metastasis; AlloStim®; cryoablation; cancer vaccine; immunotherapy; MSI-S

Outcome Measures

Primary Outcomes (1)

• Evaluate the Overall Survival

  Subjects are followed for survival monthly after completion of dosing

  from time of signing informed consent for up to 18 months or until death

Study Arms (2)

Dosing Schedule A (with cryoablation)

EXPERIMENTAL

* The priming step with ID injections of AlloStim on Days 0, 7, and 14 * The vaccination step with cryoablation and IT (intratumoral) injection of AlloStim on Day 21 * The activation step with IV infusion of AlloStim on Day 28 * The booster step with two IV booster infusions of AlloStim on Days 56 and 84 Protocol follow-up procedures continue until day 112. Efficacy evaluation will continue monthly for each subject until death or loss to follow-up

Biological: AlloStim; Procedure: Cryoablation

Dosing Schedule B without cryoablation

EXPERIMENTAL

The priming step with ID injections of AlloStim on Days 0, 3, 7, 10 and day 14 * IV AlloStim on Day 21 * The booster step with two IV booster infusions of AlloStim on Days 49 and 77 Protocol follow-up procedures continue until day 105. Efficacy evaluation will continue monthly for each subject until death or loss to follow-up Protocol follow-up procedures continue until day 105. Efficacy evaluation will continue monthly for each subject until death or loss to follow-up

Biological: AlloStim

Interventions

AlloStim BIOLOGICAL

AlloStim is an activated living CD4+ Th1 memory cell derived from the blood of normal blood donors and intentionally mismatched to the recipient. AlloStim is bioengineered to express high levels of Type 1 inflammatory cytokines (such as interferon-gamma, TNF-alpha, GM-CSF) and immunomodulatory molecules such as CD40L. AlloStim has CD3/CD28-coated microbeads attached to assure activation upon infusion.

Also known as: CryoVax

Dosing Schedule A (with cryoablation); Dosing Schedule B without cryoablation

Cryoablation PROCEDURE

Percutaneous partial cryoablation of a single metastatic tumor lesion in the liver. The procedure is conducted under CT or ultrasound image-guidance

Dosing Schedule A (with cryoablation)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males and female subjects aged 18-80 years at screening visit
• Pathologically confirmed diagnosis of colorectal adenocarcinoma
• Presenting with metastatic disease:
• Primary can be intact or previously resected
• Metastatic lesion(s) in liver must be non-resectable
• Extrahepatic disease acceptable
• At least one liver lesion able to be visualized by ultrasound and determined to be safely assessable for percutaneous cryoablation
• Previous treatment failure of two previous lines of active systemic chemotherapy:
• Previous chemotherapy must have included an oxaliplatin-containing (e.g. FOLFOX) and an irinotecan-containing (e.g. FOLFIRI) regimen
• with or without bevacizumab
• administered in adjuvant setting or for treatment of metastatic disease
• If KRAS wild type, must have at least one prior anti-EGFR therapy
• Treatment failure can be due to disease progression or toxicity
• Disease progression on second line therapy must be documented radiologically and must have occurred during or within 30 days following the last administration of treatment for metastatic disease
• ECOG performance score: 0-1

You may not qualify if:

• Bowel obstruction or high risk for obstruction
• Moderate or severe ascites requiring medical intervention
• Clinical evidence or radiological evidence of brain metastasis or leptomeningeal involvement
• Symptomatic asthma or COPD
• Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in pulmonary dysfunction requiring active treatment or oxygen saturation \<92% on room air
• Bevacizumab (Avastin®) treatment within 6 weeks of scheduled cryoablation procedure
• Regorafenib prior to the Study Period
• Taking anticoagulant medication for concomitant medical condition (unless can be safely discontinued for invasive cryoablation, biopsy and intratumoral injection procedures)
• Prior allogeneic bone marrow/stem cell or solid organ transplant
• Chronic use (\> 2 weeks) of greater than physiologic doses of a corticosteroid agent (dose equivalent to \> 5 mg/day of prednisone) within 30 days of the first day of study drug treatment
• Topical corticosteroids are permitted
• Prior diagnosis of an active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, autoimmune thyroid disease, uveitis). Well controlled Type I diabetes allowed
• Prior experimental therapy
• History of blood transfusion reactions
• Known allergy to bovine products

Sponsors & Collaborators

• Mirror Biologics, Inc.: lead

Study Sites (1)

Banner MD Anderson Medical Center

Gilbert, Arizona, 85234, United States

Location

Related Publications (8)

• Epple LM, Bemis LT, Cavanaugh RP, Skope A, Mayer-Sonnenfeld T, Frank C, Olver CS, Lencioni AM, Dusto NL, Tal A, Har-Noy M, Lillehei KO, Katsanis E, Graner MW. Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine. Int J Hyperthermia. 2013 Aug;29(5):390-8. doi: 10.3109/02656736.2013.800997. Epub 2013 Jun 20.

  PMID: 23786302 BACKGROUND

• Mayer-Sonnenfeld T, Har-Noy M, Lillehei KO, Graner MW. Proteomic analyses of different human tumour-derived chaperone-rich cell lysate (CRCL) anti-cancer vaccines reveal antigen content and strong similarities amongst the vaccines along with a basis for CRCL's unique structure: CRCL vaccine proteome leads to unique structure. Int J Hyperthermia. 2013 Sep;29(6):520-7. doi: 10.3109/02656736.2013.796529. Epub 2013 Jun 4.

  PMID: 23734882 BACKGROUND

• LaCasse CJ, Janikashvili N, Larmonier CB, Alizadeh D, Hanke N, Kartchner J, Situ E, Centuori S, Har-Noy M, Bonnotte B, Katsanis E, Larmonier N. Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-gamma-dependent mechanism. J Immunol. 2011 Dec 15;187(12):6310-7. doi: 10.4049/jimmunol.1101812. Epub 2011 Nov 9.

  PMID: 22075702 BACKGROUND

• Janikashvili N, LaCasse CJ, Larmonier C, Trad M, Herrell A, Bustamante S, Bonnotte B, Har-Noy M, Larmonier N, Katsanis E. Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia. Blood. 2011 Feb 3;117(5):1555-64. doi: 10.1182/blood-2010-06-288621. Epub 2010 Dec 1.

  PMID: 21123824 BACKGROUND

• Har-Noy M, Zeira M, Weiss L, Fingerut E, Or R, Slavin S. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma. Leuk Res. 2009 Apr;33(4):525-38. doi: 10.1016/j.leukres.2008.08.017. Epub 2008 Oct 1.

  PMID: 18834631 BACKGROUND

• Har-Noy M, Zeira M, Weiss L, Slavin S. Completely mismatched allogeneic CD3/CD28 cross-linked Th1 memory cells elicit anti-leukemia effects in unconditioned hosts without GVHD toxicity. Leuk Res. 2008 Dec;32(12):1903-13. doi: 10.1016/j.leukres.2008.05.007. Epub 2008 Jun 18.

  PMID: 18565579 BACKGROUND

• Har-Noy M, Slavin S. The anti-tumor effect of allogeneic bone marrow/stem cell transplant without graft vs. host disease toxicity and without a matched donor requirement? Med Hypotheses. 2008;70(6):1186-92. doi: 10.1016/j.mehy.2007.10.008. Epub 2007 Dec 3.

  PMID: 18054441 BACKGROUND

• Zeng Y, Stokes J, Hahn S, Hoffman E, Katsanis E. Activated MHC-mismatched T helper-1 lymphocyte infusion enhances GvL with limited GvHD. Bone Marrow Transplant. 2014 Aug;49(8):1076-83. doi: 10.1038/bmt.2014.91. Epub 2014 Apr 28.

  PMID: 24777185 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Cryosurgery

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Michael Har-Noy
• Organization: Mirror Biologics, Inc

harnoy@mirrorbio.com

7602167494

Study Officials

• Madappa Kundranda, MD PHD

  Banner MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 5, 2015
• Study Start: September 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: September 1, 2018
• Last Updated: May 16, 2025
• Results First Posted: May 16, 2025

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)