KEY TAKEAWAYS
- The phase 1 study explored Cami alone and with Pembrolizumab for treatment efficacy in selected advanced solid tumor patients.
- Primary aim: Safety in monotherapy and combination treatment; secondary aim: Assess antitumor activity.
- Cami’s monotherapy showed good tolerance without major safety concerns. However, the Cami-pembrolizumab combo raised skin/immune-related adverse events.
Camidanlumab tesirine (Cami) is a treatment composed of an anti-CD25 antibody linked to a pyrrolobenzodiazepine dimer cytotoxin. It reduces CD25+ regulatory T cells (Tregs) and enhances the balance between CD8+ cytotoxic T-lymphocytes (CTLs) and Tregs within tumors. For this study, researchers evaluated the clinical findings and biomarker information from a phase 1 clinical trial involving Cami used alone and in conjunction with pembrolizumab.
The primary objective was to assess the safety and tolerance of both single and combined treatments among patients aged 18 and above dealing with specific advanced solid tumors after exhausting standard therapies. Secondary objectives involved studying early signs of treatment effectiveness, drug levels in the body, biomarkers, and immune responses. Both single and combined therapy used a 3+3 design for dose escalation.
As a single treatment, patients received Camidanlumab tesirine (Cami) at increasing doses every 3 weeks. For the combined treatment, patients received pembrolizumab 200mg every 3 weeks per cycle and Cami every 3 weeks for 2 out of every 4 cycles (alternating 2 cycles with Cami and 2 cycles without) at increasing doses.
A total of 44 patients underwent Camidanlumab tesirine (Cami) treatment alone, ranging from doses of 20ug/kg to 150ug/kg as of data till December 22, 2022. No dose-limiting toxicities (DLTs) were observed, and the maximum tolerated dose (MTD) was not determined. The most frequent severe adverse events (AEs) of grade 3 or higher, regardless of their relation to treatment, included anemia (9.1%), abdominal pain, pulmonary embolism, and rash (6.8% each). Stable disease (SD) was noticed in 25% of patients.
In the combination treatment involving 34 patients, doses ranged from 30ug/kg to 100ug/kg. Two DLTs were reported: one grade 3 pneumonitis and one grade 3 pancreatitis. The MTD remained undetermined. Severe AEs of grade 3 or higher, irrespective of their association, included maculo-papular rash (17.6%), anemia (14.7%), hyponatremia, and decreased lymphocyte count (11.8% each).
The disease control rate (DCR) for the combination group stood at 45.5%, which included one complete response, 4 partial responses, and 10 cases of stable disease. Among the heavily treated ovarian cancer patients (median prior therapy lines: 4), 5 responses and 3 instances of stable disease were observed (ORR 28%, DCR 44%).
The balance between CTLs and Tregs showed alterations consistent with Cami’s anticipated mechanism of action. Data regarding biomarkers in both blood circulation and the tumor microenvironment will be presented and correlated with efficacy data.
Cami, when used alone, demonstrated good tolerance without significant safety concerns. When combined with pembrolizumab, there’s an observed rise in skin-related and irAEs. Despite this, the combination exhibits promising outcomes among heavily treated ovarian cancer patients.
Source: https://jitc.bmj.com/content/11/Suppl_1/A692
Clinical Trial: https://clinicaltrials.gov/study/NCT03621982
Panchabhai S, Ernstoff MS, Hamid O, et al740 Pattern of natural killer (NK) cell (CD16+CD56+) expansion correlates with response outcomes with nemvaleukin alfa treatmentJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0740.
