What is tremelimumab-actl?
Tremelimumab is an anti-CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) monoclonal antibody. It works by inhibiting the binding of CTLA-4 and blocking the interaction with its ligands CD80 and CD86 leading to inhibition of T-cell activation.
What is tremelimumab-actl approved for?
Tremelimumab is FDA-approved for treatment of unresectable hepatocellular carcinoma (HCC) and metastatic non-small cell lung cancer (NSCLC). It was approved for treatment of HCC based on the STRIDE trial (NEJM Evid 2022; https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100070). This was an open-label, Phase III trial comparing single-agent durvalumab, sorafenib, and the STRIDE regimen (single tremelimumab regular interval durvalumab).
The outcomes of this trial showed an overall survival (OS) at 36 months of 30.7 percent (STRIDE), 24.7 percent (durvalumab), and 20.2 percent (sorafenib), concluding that STRIDE significantly improved OS versus sorafenib and finding durvalumab monotherapy to be noninferior to sorafenib.
The POSEIDON trial was an open-label, Phase III trial evaluating tremelimumab plus durvalumab plus chemotherapy (T+D+CT) versus durvalumab plus chemotherapy (D+CT) versus chemotherapy alone (CT) in frontline metastatic NSCLC (J Clin Oncol 2023; doi:10.1200/JCO.22.00975). Outcomes from this trial found the progression-free survival to be 6.2 versus 4.8 months, and 24-month OS of 32.9 percent versus 22.1 percent, which were significantly improved comparing T+D+CT and CT. There was no meaningful addition of adverse events with the addition of tremelimumab and durvalumab to chemotherapy.
How do you administer tremelimumab-actl?
Tremelimumab is infused over 60 minutes. It is recommended to observe the patient for at least 60 minutes following first infusion prior to infusing durvalumab.
* HCC: Administered as a 300 mg dose on Cycle 1 Day 1 in combination with durvalumab. In patients less than 30 kg weight-based dosing of 4 mg/kg instead of flat dose.
* NSCLC: Tremelimumab 75 mg every 3 weeks administered in combination with durvalumab and standard-of-care platinum-based chemotherapy for 4 cycles and then in combination with durvalumab (+/- maintenance chemotherapy) for Cycle 6 only. There is a 4-week interval between Cycle 5 and 6. Tremelimumab is not administered during Cycle 5. In patients less than 30 kg, there is weight-based dosing of 1 mg/kg instead of flat dose. Tremelimumab is administered for a total of up to 5 doses.
Are there any pre-medications needed?
Tremelimumab has a low emetic risk. No routine pre-medications are recommended.
What are the common side effects (> or =20%)?
The most common adverse events were an increase in AST/ALT, an increase in alkaline phosphatase or bilirubin, skin rash, fatigue, diarrhea, anemia, thrombocytopenia, increase in serum creatinine, and electrolyte abnormalities.
What are the uncommon side effects (less than 20%)?
Nausea, vomiting, decreased appetite, fever, and infusion-related reactions.
What are serious warning and precautions for tremelimumab-actl?
The risk of immune-mediated toxicities exists with tremelimumab. These immune-mediated toxicities can be serious and include pneumonitis, colitis, hepatitis, multiple endocrinopathies, etc.
Are there any important drug interactions I should be aware of?
Coadministration with corticosteroids may diminish therapeutic effects of immune checkpoint inhibitors.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
No dose adjustments are provided for those with mild or moderate renal or hepatic dysfunction prior to treatment initiation. Patients experiencing renal or hepatic toxicity during treatment should be assessed for immune-mediated toxicities and managed as indicated per guidelines.
What should my patients know about tremelimumab-actl?
* Pregnancy should be avoided due to the risk for embryo-fetal toxicity and both men and women should use effective contraception during treatment and at least 3 months following the last dose.
* Breastfeeding should be avoided during treatment and at least 3 months after the last dose.
Any ongoing clinical trials related?
Tremelimumab is also being studied in clinical trials of various phases and combinations in patients with advanced cancers. More information is available about these trials at http://clinicaltrials.gov.
SASHA HAARBERG, PHARMD, BCOP, is Clinical Oncology Pharmacist at Siteman Cancer Center and Washington University School of Medicine. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.
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