Clinical trials with zanidatumab revealed significant diarrhea primarily in the first cycle. The successful management strategy involves mandatory loperamide twice daily for the first seven days to improve tolerability and prevent treatment discontinuation, a crucial implementation pearl.

A novel trial design used mosinutuzumab monotherapy first in frontline follicular lymphoma, adding lenalidomide only for patients without a complete response. This adaptive approach successfully spared about two-thirds of patients from the added toxicities of lenalidomide while still achieving very high overall efficacy.

Real-world data suggests that using one antibody-drug conjugate (ADC) immediately after another is often ineffective. A potential strategy to overcome this resistance is to administer a different class of chemotherapy before starting the second ADC.

In the SPOTLIGHT trial, adding zolbituximab to FOLFOX for Claudin-18.2 positive patients improved progression-free and overall survival. However, it did not significantly increase the objective response rate, demonstrating that survival benefit can be decoupled from tumor shrinkage metrics.

An expert argues the path to curing metastatic cancer may mirror pediatric ALL's history: combining all highly active drugs upfront. Instead of sequencing treatments after failure, the focus should be on powerful initial regimens that eradicate cancer, even if it means higher initial toxicity.

For patients over 75 with metastatic gastric cancer, a common practice is to reduce the oxaliplatin dose from 85 to 65 mg/m² and universally omit the 5-FU bolus from the FOLFOX regimen. This pragmatic approach aims to maintain efficacy while minimizing toxicity in a more vulnerable population.

With highly active agents yielding 30% complete response rates, the immediate goal should be to cure more patients by exploring potent combinations upfront. While sequencing minimizes toxicity, an ambitious combination strategy, such as ADC doublets, offers the best chance to eradicate disease and should be prioritized in clinical trials.

The HORIZON-GEA-01 trial for zanidatumab in gastric cancer mandated prophylactic loperamide (4mg BID) for all patients. This was necessary to manage the high rates of diarrhea (up to 80% of patients), a significant GI toxicity associated with the drug's mechanism of action.

Actuate employed a master protocol that tested their drug alongside eight different standard-of-care chemotherapies in patients who had already failed them. This design efficiently demonstrated the drug's ability to reverse chemo-resistance across multiple histologies, informing their Phase 2 strategy.