IMX-110 Plus Tislelizumab Shows Early Activity in Advanced Metastatic Colorectal Cancer

Treatment with the combination of IMX-110 and tislelizumab (BGB-A317) resulted in 100% tumor shrinkage at 2 months in 2 of 2 evaluable patients with advanced metastatic colorectal cancer (mCRC) who received the regimen at the lowest dose level examined in the dose-escalation portion of the ongoing phase 1b/2a IMMINENT-01 trial (NCT05840835).¹

The early interim clinical data had a cutoff date of April 14, 2023. At this time point, dosing for the first cohort of 3 patients with advanced mCRC had been completed.

Since no dose-limiting toxicities were observed, the trial is slated to enroll the next cohort of patients with advanced solid tumors (n = 3) who will receive IMX-110 at a higher dose in combination with tislelizumab.

“We are excited to see 100% tumor shrinkage in the very first cohort at the lowest dose of IMX-110 in combination with [the] anti–PD-1 antibody tislelizumab in our ongoing IMMINENT-01 dose-escalation trial, especially in patients with advanced CRC, who have limited treatment options,” Ilya Rachman, MD, PhD, chief executive officer of ImmixBio, stated in a press release. “These initial results potentially validate the scientific rationale for the promise of IMX-110 to unlock our immune system’s ability to fight cancer.”

Preclinical data revealed that when the doublet was administered to a genetic pancreatic cancer mouse model, it resulted in an extended median survival of 63 days.² According to Immix Biopharma, historically, a 4-drug combination comprised of gemcitabine and nab-paclitaxel (Abraxane), as well as anti–PD-1 and anti–CD40 agents, had resulted in a median survival of 42 days in the same genetic model.

For the open-label, multicenter, early-phase trial, investigators enrolled patients with a confirmed advanced solid tumor whose disease had progressed, was refractory, or was intolerant to standard treatment.³ To be eligible for enrollment, patients were required to be at least 16 years of age, have an ECOG performance status of 0 to 2, a life expectancy of at least 3 months, and acceptable cardiac function, among other criteria.

Those who received immunotherapy within 28 days of study dosing, a biologic or hormonal therapy within 28 days of dosing, or chemotherapy within 14 days of dosing, were excluded, as were those who participated in any other drug study within 4 weeks of treatment. If patients had a history of severe allergic reactions to any components of the study drugs or a history of and/or risk factors for ischemic heart disease, they were excluded.

In the phase 1b portion of the research, cohorts of 3 patients are receiving escalating doses of IMX-110 until the maximum tolerated dose (MTD) is identified, and the recommended phase 2 dose (RP2D) is determined.1,2 Based on data on several tumor types collected in phase 1b, phase 2a will begin treating patients with certain solid tumor indications with the doublet.

Identifying the MTD and RP2D of IMX-110 for use in combination with tislelizumab serves as the trial’s primary end point. Key secondary end points include examining the preliminary efficacy in the form of response rate, duration of response, progression-free survival, and overall survival, as well as the pharmacokinetics of the combination.

In February 2023, it was announced that the first 2 patients with advanced solid tumors who were enrolled to the trial were dosed with the regimen.⁴

Thirty total participants are anticipated to enroll on the trial, and patients are currently being enrolled to the next higher dose cohort.

In September 2021, the FDA granted IMX-110 an orphan drug designation for the treatment of patients with soft tissue sarcoma.⁵

References

1. Immix Biopharma announces early positive IMX-110 interim clinical trial data demonstrating 100% tumor shrinkage in advanced metastatic colorectal cancer at the lowest dose of IMX-110 + BeiGene / Novartis anti-PD-1 antibody tislelizumab. News release. Immix Biopharma, Inc. May 3, 2023. Accessed May 3, 2023. https://immixbio.com/2023/05/03/
2. IMX-110 + anti-PD-1 combination produced extended median survival in genetic pancreatic cancer mouse model, bolstering planned 2022 IMX-110 combination clinical trial rationale. News release. January 25, 2022. Accessed May 3, 2023. https://immixbio.com/2022/01/25/
3. Study of IMX-110 in combination with tislelizumab in patients with advanced solid tumors. ClinicalTrials.gov. Updated May 3, 2023. Accessed May 3, 2023. https://clinicaltrials.gov/ct2/show/NCT05840835
4. Immex Biopharma announces dosing of first 2 patients in its IMX-110 + BeiGene/Novartis anti-PD-1 tislelizumab phase 1b/2a combination clinical trial in patients with advanced cancer. News release. Immix Biopharma, Inc. February 7, 2023. Accessed May 3, 2023. https://immixbio.com/2023/02/07/
5. ImmixBio announces FDA orphan drug designation for IMX-110 for the treatment of soft tissue sarcoma. News release. Immix Biopharma, Inc. September 30, 2021. Accessed May 3, 2023. https://www.prnewswire.com/news-releases/