A Phase 2 Study of Saltikva (Attenuated Salmonella Typhimurium Containing the Human Gene for Interleukin-2) in Patients With Metastatic Pancreatic Cancer

Objectives: Assess the efficacy of multiple dose oral administration of Saltikva, an attenuated strain of Salmonella Typhimurium expressing IL-2, in patients with metastatic pancreatic cancer on standard chemotherapy (either FOLFIRINOX or Gemcitabine/Abraxane and Saltikva).
Study Rationale: The addition of Saltikva to the standard of care regimen for Stage IV metastatic pancreatic cancer will significantly prolong the overall survival and prolong the time to disease progression.
Patient Population: unresectable, metastatic pancreatic cancer patients 18 years of age or older

Start Date20 Oct 2020

Sponsor / Collaborator

Salspera LLC

100 Clinical Results associated with Saltikva

100 Translational Medicine associated with Saltikva

100 Patents (Medical) associated with Saltikva

Literatures (Medical) associated with Saltikva

09 Oct 2023·JCI insight

Overcoming lung cancer immunotherapy resistance by combining nontoxic variants of IL-12 and IL-2.

Article

Author: Spranger, Stefani ; D'Souza, Alicia D ; Momin, Noor ; Sheen, Allison ; Agarwal, Yash ; Wittrup, K Dane ; Horton, Brendan L ; White, Forest M ; Picton, Lora ; McCreery, Chloe V ; Abhiraman, Gita C ; Zagorulya, Maria ; Garcia, K Christopher

Engineered cytokine-based approaches for immunotherapy of cancer are poised to enter the clinic, with IL-12 being at the forefront. However, little is known about potential mechanisms of resistance to cytokine therapies. We found that orthotopic murine lung tumors were resistant to systemically delivered IL-12 fused to murine serum albumin (MSA, IL12-MSA) because of low IL-12 receptor (IL-12R) expression on tumor-reactive CD8+ T cells. IL2-MSA increased binding of IL12-MSA by tumor-reactive CD8+ T cells, and combined administration of IL12-MSA and IL2-MSA led to enhanced tumor-reactive CD8+ T cell effector differentiation, decreased numbers of tumor-infiltrating CD4+ regulatory T cells, and increased survival of lung tumor-bearing mice. Predictably, the combination of IL-2 and IL-12 at therapeutic doses led to significant dose-limiting toxicity. Administering IL-12 and IL-2 analogs with preferential binding to cells expressing Il12rb1 and CD25, respectively, led to a significant extension of survival in mice with lung tumors while abrogating dose-limiting toxicity. These findings suggest that IL-12 and IL-2 represent a rational approach to combination cytokine therapy whose dose-limiting toxicity can be overcome with engineered cytokine variants.

01 Sep 2023·Journal of neurology

A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing-remitting multiple sclerosis.

Article

Author: Louapre, C ; Klatzmann, D ; Rosenzwajg, M ; Charbonnier-Beaupel, F ; Lubetzki, C ; Ungureanu, A ; Papeix, C ; Golse, M ; Roux, A ; Maillart, E ; Galanaud, D ; Adda, L ; Corvol, J C ; Pitoiset, F ; Vicaut, E ; Tchitchek, N

BACKGROUNDMultiple sclerosis (MS) is associated with regulatory T cells (Tregs) insufficiency while low-dose interleukin-2 (IL2_LD) activates Tregs and reduces disease activity in autoimmune diseases.METHODSWe aimed at addressing whether IL2_LD improved Tregs from MS patients. MS-IL2 was a single-center double-blind phase-2 study. Thirty patients (mean [SD] age 36.8 years [8.3], 16 female) with relapsing-remitting MS with new MRI lesions within 6 months before inclusion were randomly assigned in a 1:1 ratio to placebo or IL-2 at 1 million IU, daily for 5 days and then fortnightly for 6 months. The primary endpoint was change in Tregs at day-5.RESULTSUnlike previous trials of IL2_LD in more than 20 different autoimmune diseases, Tregs were not expanded at day-5 in IL2_LD group, but only at day-15 (median [IQR] fold change from baseline: 1.26 [1.21-1.33] in IL2_LD group; 1.01 [0.95-1.05] in placebo group, p < 0.001). At day-5, however, Tregs had acquired an activated phenotype (fold change of CD25 expression in Tregs: 2.17 [1.70-3.55] in IL2_LD versus 0.97 [0.86-1.28] in placebo group, p < 0.0001). Regulator/effector T cells ratio remained elevated throughout treatment period in the IL2_LD group (p < 0.001). Number of new active brain lesions and of relapses tended to be reduced in IL2_LD treated patients, but the difference did not reach significance in this trial not powered to detect clinical efficacy.CONCLUSIONThe effect of IL2_LD on Tregs in MS patients was modest and delayed, compared to other auto-immune diseases. This, together with findings that Tregs improve remyelination in MS models and recent reports of IL2_LD efficacy in amyotrophic lateral sclerosis, warrants larger studies of IL2_LD in MS, notably with increased dosages and/or modified modalities of administration.TRIAL REGISTRATION INFORMATIONClinicalTrials.gov: NCT02424396; EU Clinical trials Register: 2014-000088-42.

01 Sep 2020·Journal of ImmunotherapyQ4 · MEDICINE

A Phase I, Dose Escalation, Single Dose Trial of Oral Attenuated Salmonella typhimurium Containing Human IL-2 in Patients With Metastatic Gastrointestinal Cancers

Q4 · MEDICINE

Article

Author: Schottel, Janet ; Batist, Gerald ; Greeno, Edward ; Saltzman, Daniel ; Augustin, Lance ; Gniadek, Thomas J ; Leonard, Arnold

Salmonella has been shown to preferentially colonize solid tumors. It is known that toxicity limits the systemic administration of immunomodulatory cytokines that have a significant anticancer effect. Therefore, we tested a unique cancer treatment strategy comprised of oral delivery of Saltikva, an attenuated strain of Salmonella typhimurium that contain the human gene for interleukin-2. In preclinical experimentation, a significant antitumor effect without toxicity was observed. A dose escalation, single dose, Phase I trial was conducted. Dose escalation (105 to 1010) while monitoring for dose limiting toxicity and response was performed. Flow cytometry was conducted to determine the immunologic effect. In total 22 patients were administered Saltikva. Eight patients did not complete the trial. No toxicity or adverse events were observed. There was no survival advantage. Flow cytometry demonstrated an increase in circulating natural killer (NK) cells and NK-T cells when comparing the prestudy period. The results of this phase I dose escalation study show that oral attenuated S. typhimurium containing the human interleukin-2 gene caused no significant toxicities up to doses of 1010 colony forming unit. There was no evidence of partial or complete response. All patients had progressive disease and eventually succumbed to their illness. Although no survival advantage was seen in this single dose study, the statistically significant increase in circulating NK and NK-T cell demonstrates an immunologic effect from this treatment regimen and suggest that a multiple dose study should be undertaken.

100 Deals associated with Saltikva

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Cancer	Phase 1	CA	-	19 Oct 2020
Gastrointestinal Neoplasms	Discovery	US	Salspera LLC	16 Jun 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


AACR2023 Manual	Phase 2	Secondary malignant neoplasm of pancreas	20	Saltikva+FOLFIRINOX	(nunzrcsnmc) = pdghebwcjk ouvsoklxtt (sqrvrdkoif ) View more	Positive	14 Apr 2023
				FOLFIRNOX (published historical controls)	(nunzrcsnmc) = wmljhouimg ouvsoklxtt (sqrvrdkoif ) View more

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