KEY TAKEAWAYS
- Two phase-2 studies, ELEVATE TNBC, and ELEVATE Lung&UC, aimed to assess the safety/tolerability of magrolimab in combination with taxanes in mTNBC and mNSCLC/mSCLC.
- Safety aligned with known toxicity profiles. Magrolimab was well-tolerated in combinations; no severe issues or unexpected signals were observed.
Two Phase 2 studies (ELEVATE TNBC: NCT04958785; ELEVATE Lung&UC: NCT04827576) assessed magrolimab’s safety and recommended Phase 2 dose (RP2D) when combined with taxanes in advanced triple-negative breast cancer, lung cancers (non-small cell and small cell), and urothelial cancer. The researchers shared and evaluated data from two safety run-ins (SRIs) in these trials for this study.
In the first safety run-in (SRI1), patients (pts) with advanced triple-negative breast cancer (TNBC) received magrolimab combined with nanoparticle albumin-bound-paclitaxel or paclitaxel. Patients with advanced non-small cell/small cell lung cancers (mNSCLC/mSCLC) or urothelial cancer in the second safety run-in (SRI2) received magrolimab with docetaxel.
Magrolimab dosing began with a 1 mg/kg initial dose, followed by either 7 weeks of 30 mg/kg weekly (SRI1) or 5 weeks (SRI2), followed by maintenance doses. Chemo was administered according to standard care. Safety assessments were conducted on pts who received at least one dose of any study drug.
Dose-limiting toxicities (DLTs) were evaluated in pts who either experienced a DLT during the evaluation period or completed specified doses of magrolimab and taxane. To determine the recommended Phase 2 dose (RP2D), the study allowed ≤2 of 6 DLT-evaluable pts to experience a DLT, or dosage adjustments would be made for magrolimab with reassessment.
In each safety run-in (SRI), 6 patients were considered for assessing dose-limiting toxicities (DLTs). The analysis involved 8 patients in SRI1 and 9 in SRI2. No DLTs occurred during the assessment period. Treatment-emergent adverse events (TEAEs) were noted in 8 patients in SRI1 and 9 in SRI2.
In SRI1, common TEAEs included anemia, vomiting, and headache (5 occurrences each), while fatigue (5 occurrences) and hyponatremia (3 occurrences) were prominent in SRI2. Two patients in SRI2 stopped magrolimab due to TEAEs (fatal gastrointestinal bleed [deemed unrelated] and grade 3 neuritis). No additional deaths were recorded.
The safety profile aligned with the anticipated effects of the agents involved, suggesting the tolerability of magrolimab in these combinations. No dose-limiting toxicities, deaths linked to magrolimab, or unexpected safety concerns were noted in any of the indications.
Source: https://jitc.bmj.com/content/11/Suppl_1/A792
Clinical Trial: https://clinicaltrials.gov/study/NCT04958785
https://clinicaltrials.gov/study/NCT04827576
Juan-Videl O, Chiu J, Vaishampayan UN, et al698 Safety and tolerability of magrolimab in combination with taxanes in patients with solid tumorsJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0698
