Abstract | BACKGROUND: METHODS: Adults (n=27) with advanced solid tumors (naive to PD-L1/ programmed cell death protein 1 or CTLA-4 inhibitors) were enrolled in the phase 1 combination therapy dose-escalation portion of this multicenter, open-label, phase 1/2 study (NCT03013491). Dose-escalation pacmilimab/ ipilimumab followed a standard 3+3 design and continued until the maximum tolerated dose (MTD) was determined. Pacmilimab+ipilimumab was administered intravenously every 3 weeks for four cycles, followed by pacmilimab administered every 2 weeks as monotherapy. The primary objective was identification of dose-limiting toxicities and determination of the MTD. Other endpoints included the rate of objective response (Response Evaluation Criteria In Solid Tumors v.1.1). RESULTS: Twenty-seven patients were enrolled in pacmilimab (mg/kg)+ ipilimumab (mg/kg) dose-escalation cohorts: 0.3+3 (n=6); 1+3 (n=3); 3+3 (n=3); 10+3 (n=8); 10+6 (n=6); and 10+10 (n=1). Dose-limiting toxicities occurred in three patients, one at the 0.3+3 dose level (grade 3 dyspnea/ pneumonitis) and two at the 10+6 dose level (grade 3 colitis, grade 3 increased aspartate aminotransferase). The MTD and recommended phase 2 dose was pacmilimab 10 mg/kg+ipilimumab 3 mg/kg administered every 3 weeks. Pacmilimab-related grade 3-4 adverse events (AEs) and grade 3-4 immune-related AEs were reported in nine (33%) and six (22%) patients, respectively. Three patients (11%) discontinued treatment because of AEs. The overall response rate was 19% (95% CI 6.3 to 38.1), with one complete (anal squamous cell carcinoma) and four partial responses ( cancer of unknown primary, leiomyosarcoma, mesothelioma, testicular cancer). Responses lasted for >12 months in four patients. CONCLUSIONS: The MTD and recommended phase 2 dose of pacmilimab (10 mg/kg)+ ipilimumab (3 mg/kg) every 3 weeks is active and has a favorable tolerability profile.
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Authors | Rachel E Sanborn, Omid Hamid, Elisabeth Ge de Vries, Patrick A Ott, Javier Garcia-Corbacho, Valentina Boni, Johanna Bendell, Karen A Autio, Daniel C Cho, Ruth Plummer, Mark Stroh, Lawrence Lu, Fiona Thistlethwaite |
Journal | Journal for immunotherapy of cancer
(J Immunother Cancer)
Vol. 9
Issue 7
(07 2021)
ISSN: 2051-1426 [Electronic] England |
PMID | 34301808
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
Chemical References |
- Antibodies, Monoclonal
- B7-H1 Antigen
- CD274 protein, human
- Immune Checkpoint Inhibitors
- Ipilimumab
- Prodrugs
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- B7-H1 Antigen
(antagonists & inhibitors, immunology)
- Dose-Response Relationship, Drug
- Female
- Humans
- Immune Checkpoint Inhibitors
(administration & dosage)
- Immunotherapy
- Ipilimumab
(administration & dosage)
- Male
- Middle Aged
- Neoplasms
(drug therapy, immunology)
- Prodrugs
(administration & dosage)
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