Exelixis and Bristol-Myers Squibb Expand Collaboration to Investigate Nivolumab/Relatlimab/XL092 in STELLAR-002

Exelixis, Inc has expanded their clinical trial collaboration and supply agreement with Bristol-Myers Squibb to evaluate the novel triplet of nivolumab, relatlimab, and XL092 in the phase 1b STELLAR-002 trial.

A clinical trial collaboration and supply agreement between Exelixis, Inc and Bristol-Myers Squibb Company will expand to include the use of the fixed-dose combination of nivolumab and relatlimab (Opdualag) in the ongoing phase 1b STELLAR-002 clinical trial (NCT05176483) evaluating XL092 in combination with multiple immune checkpoint inhibitors (ICIs) in advanced solid tumors.1

Exelixis, Inc is sponsoring the STELLAR-002 trial while Bristol-Myers Squibb will be providing the fixed-dose combination of nivolumab plus relatlimab in addition to nivolumab and ipilimumab (Yervoy) for use in the trial. The study is divided into 2 parts, including a dose-escalation portion and an expansion cohort.

Investigators hope that this novel triplet combination of XL092 plus the fixed-dose combination of nivolumab and relatlimab will show potential for the treatment of patients in multiple expansion cohorts.

“We are pleased to expand our agreement with Bristol Myers Squibb for the STELLAR-002 trial to include the novel fixed-dose combination of nivolumab and relatlimab to evaluate the potential benefit of combining XL092 with additional immune checkpoint inhibitors,” said Vicki L. Goodman, MD, executive vice president, product development & medical affairs, and chief medical officer of Exelixis, Inc, in the press release. “By studying multiple immune checkpoint combinations, we hope to identify the most promising regimens across multiple solid tumors to use in future pivotal trials.”

XL092 is a next-generation, oral tyrosine kinase inhibitor (TKI) working to target the MET, AXL, and MER VEGF receptors, as well as other kinases implicated in the growth and spread of cancer. Relatlimab is a lymphocyte activation gene-3 (LAG-3)-blocking antibody. LAG-3 is an inhibitory immune checkpoint expressed on the surface of T cells.

Both enrollment and dosing in the dose-escalation part of STELLAR-002 is ongoing. The goal of this dose-escalation portion of the trial is to determine the recommended dose in patients with advanced solid tumors for each of the combination therapy regimens. These include XL092 and nivolumab, XL092, nivolumab and ipilimumab, and XL092 and the fixed-dose combination of nivolumab and relatlimab.

STELLAR-002 is a multicenter, open label, phase 1b, dose-escalation and cohort-expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect of biomarkers of XL092 when administered alone and in combination with nivolumab, and nivolumab plus ipilimumab in patients with advanced solid tumors.2

The trial aims to enroll 622 patients aged 18 years and older with a cytologically or histologically confirmed solid tumor that is unresectable, locally advanced, or metastatic.

In the dose-escalation portion of the study, patients must have a solid tumor that is unresectable or metastatic, and life-prolonging therapies or available therapies must not exist, are intolerable, or are no longer effective.

In expansion cohorts 1 and 2, patients with unresectable advanced or metastatic clear cell renal cell carcinoma who have not received prior systemic therapy will be enrolled. Expansion cohort 3 will enroll men with metastatic adenocarcinoma of the prostate. Expansion cohorts 4 and 5 will include patients with histologically confirmed unresectable, locally advanced, or metastatic transitional cell carcinoma of the urothelium, including the renal pelvis, ureter, urinary bladder, or urethra with cohort 4 consisting of patients who are immune checkpoint inhibitor (ICI)-naive and cohort 5 patients are ICI-experienced. Then, expansion cohort 6 will include patients with unresectable advanced or metastatic non-clear cell renal cell carcinoma the papillary, unclassified RCC, or translocation-associated subtype.

An additional requirement for all expansion cohorts excluding cohort 3 is measurable disease per RECIST 1.1 as determined by the investigator. For all expansion cohorts, patients must have archival tumor tissue material, recovery to baseline or ≤ grade 1 Common Terminology Criteria for Adverse Events (AEs) version 5 from AES related to any prior treatments, a Karnofsky Performance Status ≥ 70%, and adequate organ and marrow function. Patients who are sexually active and fertile must agree to use highly effective methods of contraception and female patients of childbearing potential must not be pregnant at screening.

The primary end points of the trial include, the incidence and severity of AEs and serious AEs, including immune-mediated AEs, objective response rate, and progression-free survival.

References:
  1. Exelixis expands clinical trial collaboration and supply agreement with Bristol Myers Squibb to include the fixed-dose combination of nivolumab and relatlimab in combination with XL092 in phase 1b STELLAR-002 trial. News release. Exelixis, Inc. October 4, 2022. Accessed October 6, 2022. https://bit.ly/3fGcVrj
  2. Study of XL092 in combination with immuno-oncology agents in subjects with solid tumors (STELLAR-002). ClinicalTrials.gov. Updated September 16, 2022. Accessed October 6, 2022. https://clinicaltrials.gov/ct2/show/NCT05176483