Motixafortide Shows Benefit to First-Line Pancreatic Cancer Treatment in Phase 2 Trial

Image of pancreas | Image Credit: © Лилия Захарчук - stock.adobe.com

Motixafortide, a CXC4 inhibitor, shows some positive results for treatment-naïve metastatic pancreatic ductal adenocarcinoma (mPDAC) when combined with the PD-1 inhibitor cemiplimab and standard of care (SoC) chemotherapy treatments gemcitabine and nab-paclitaxel (MCGN), phase 2 data from the CheMo4METPANC trial (NCT04543071) shows.

The data, which were published in an abstract as part of the American Association of Cancer Research (AACR) Special Conference on Pancreatic Cancer, shows that the MCGN combination can be more effective than SoC alone. The trial is the first large multicenter randomized study to evaluate this treatment combination.

"These initial data from the pilot phase of this ongoing phase 2 study give us hope that motixafortide could potentially serve as the backbone of a new treatment regimen for PDAC, which is among the most difficult cancers to treat," Philip Serlin, chief executive officer of BioLineRx Ltd, said in a press release.¹

As of May 2023, 6 out of 11 participants (55%) experienced a partial response (PR). Out of these 6, 4 (36% were confirmed PRs and 1 patient experienced resolution of a hepatic metastatic lesion. Three patients (27%) experienced stable disease, and the disease control rate (DCR) was 82%. The historic PRs and DCRs of gemcitabine and nab-paclitaxel (GN) were 23% and 48%, respectively.

The open-label, multicenter, investigator-initiated, single-arm pilot study took place at Columbia University and Brown University and began on November 9, 2020. The study planned to enroll 10 patients, but 11 patients with mPDAC were ultimately enrolled. The median age was 58. Two patients were female and 3 were Black. The primary goal was to evaluate the efficacy of MCGN on treatment-naïve mPDAC.²

Eligibility criteria included mPDAC diagnosis confirmation, adequate hematological and end-organ function within 14 days prior to study initiation, and DVT testing. Exclusion criteria included prior systemic therapy, radiation, or surgery for PDAC; unresolved adverse events (AE) from prior anti-cancer therapy; active or history of autoimmune diseases; uncontrolled pleural effusion, pericardial effusion, or ascites; and uncontrolled tumor-related pain.³

Five patients remain on the study at a median follow-up point of 9.5 months, with treatment duration ranging from 2 to 11.6 months. Four patients have stopped treatment due to disease progression, 1 patient withdrew consent, 1 was removed per physician discretion, and 5 patients have died. Nine patients in the trial have experienced grade 3 to grade 4 treatment-related AEs. These AEs include uticaria (18%) and allergic reaction, bone pain, hypertension, pain, and rash (all 9%).²

The COMBAT/KEYNOTE-202 (NCT02826486) trial evaluating the PD-1 inhibitor pembrolizumab (Keytruda) and motixafortide in combination with chemotherapy delivered a disease control rate of 77% in PDAC, suggesting motixafortide’s ability to help immunotherapy work more effectively.⁴ 

Based on the results of this trial, the study will transition to a randomized phase 2 trial with 112 participants and a primary endpoint of progression-free survival (PFS).² The study is currently recruiting participants, and the estimated study completion date is August 2025.³

REFERENCES:

1. Ltd B. BioLineRx Announces Encouraging Data from Pilot Phase of Phase 2 Combination Clinical Trial with Motixafortide in First-Line Pancreatic Cancer (PDAC). BioLineRx. September 28, 2023. Accessed October 2, 2023. https://tinyurl.com/3y37ctyc

2. Manji, GA., May, M, Chalabi, MH, et al. Presented at AACR Special Conference in Cancer Research: Pancreatic cancer; Sept 27-30, 2023; Boston, Mass.

3. CTG Labs - NCBI.Chemo4METPANC Combination Chemokine Inhibitor, Immunotherapy, and Chemotherapy in Pancreatic Adenocarcinoma.National Library of Medicine.November 11, 2022. Accessed October 2, 2023. https://clinicaltrials.gov/study/NCT04543071

4. CTG Labs - NCBI. Study Assessing Safety and Efficacy of Combination of BL-8040 and Pembrolizumab in Metastatic Pancreatic Cancer Patients (COMBAT/ KEYNOTE-202) (COMBAT). National Library of Medicine. January 4, 2023.Accessed October 2, 2023. https://clinicaltrials.gov/study/NCT02826486