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A Phase 2 Study of SX-682 in Combination with Nivolumab and Relatlimab in Melanoma Patients

Award Number: R44CA306688
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/14/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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A Phase 2 Study of SX-682 in Combination with Nivolumab and Relatlimab in Melanoma Patients - Immune-checkpoint therapies (ICTs; e.g., anti-PD1, anti-CLTLA-4, anti-LAG3) have made significant advances in treating unresectable and metastatic melanoma (Stage III/IV, together “mMEL”). However, despite the success of these immunotherapies, outcomes for mMEL remain sobering with >50% patients progressing on treatment. Median overall survival (OS) is 7.2 months after progression on anti-PD1 monotherapy (n=180) and 5.6 months after progression on ipilimumab plus nivolumab (n=67) [1]. Options are limited for the 13,000 U.S. patients progressing annually on anti-PD1 (anti-PD1 failed mMEL) who face a short median survival. The anti-PD1 failed patient population represents a significant unmet therapeutic need. Human CXCR1 and CXCR2 (CXCR1/2) are G protein-coupled receptors that promote cancer growth by (1) autocrine signaling, (2) recruiting myeloid-derived suppressors cells (MDSCs) and tumor associated neutrophils (TANs) and (3) promoting angiogenesis, tumor cell stemness, and metastasis. All CXCR1/2 ligands are significantly upregulated in human melanoma and CXCR2 tumor expression inversely correlates with survival in anti-PD1 treated melanoma patients [3]. Elevated serum CXCR1/2 ligand CXCL8 (IL-8) is associated with enhanced intratumor neutrophils and reduced overall response rate (ORR) and survival benefit of ICTs in patients with advanced cancers, including in patients with mMEL treated with nivolumab plus ipilimumab. In 297 patients with mMEL treated with nivolumab and ipilimumab, patients with serum IL-8 <23 pg/mL had (a) nearly double the ORR, (b) half the risk of progression, and (c) one-third the risk of death compared to patients with serum IL-8 ≥23 pg/mL. SX-682 is an oral, clinical-stage, potent dual CXCR1/2 allosteric inhibitor in 9 single-arm, open-label clinical trials funded by NCI, NHLBI and BMS (3 company sponsored, 6 investigator-initiated). SX-682 with pembrolizumab in anti-PD1 failed mMEL resulted in an ORR of 21% and double the historical median overall survival (OS) [5]. As of May 31, 2025, 165 patients in Syntrix-sponsored trials and at least 115 patients in investigator-initiated trials have been exposed to SX-682. The ORR of relatlimab with nivolumab (Opdualag) in anti-PD1 failed mMEL was 12% [7]. We hypothesize that SX-682 with Opdualag will provide an ORR of 30% or higher in anti-PD1 failed mMEL, allowing the trial proposed herein to position the combination for possible accelerated approval in this patient population. Through execution of the Specific Aims, we will explore this hypothesis in two patient cohorts having baseline serum IL-8 <23 pg/mL (cohort A) and IL-8 ≥23 pg/mL (cohort B), as well as for the combined cohorts A + B. Up to 55 anti-PD1 mMEL patients will be enrolled into each cohort. One of cohorts A or B may reveal a higher ORR. If successful, SX-682 added to Opdualag would transform the anti-PD1 failed mMEL treatment landscape.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $406,500 )
2026	2026	SYNTRIX BIOSYSTEMS INC.	215 CLAY ST NW	AUBURN	WA	98001	KING	USA	Cancer Treatment Research	000	1	9/14/2026	NEW	$406,053
2026	2026	SYNTRIX BIOSYSTEMS INC.	215 CLAY ST NW	AUBURN	WA	98001	KING	USA	Cancer Treatment Research	001	1	9/22/2026	NEW	$447
														Subtotal = $406,500

Grand Total All Awards = $406,500

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A Phase 2 Study of SX-682 in Combination with Nivolumab and Relatlimab in Melanoma Patients

Award Number: R44CA306688

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/14/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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