A phase 1 trial of SGN‐CD70A in patients with CD70‐positive, metastatic renal cell carcinoma

Abstract

Background Cluster of differentiation 70 (CD70) is frequently expressed in renal cell carcinoma (RCC) and has immunomodulatory properties. An antibody‐drug conjugate targeting CD70, SGN‐CD70A, was developed to treat patients with CD70‐positive RCC. Methods The objective of this phase 1, open‐label, dose‐escalation, multicenter study was to evaluate the safety and tolerability of SGN‐CD70A and establish its maximum tolerated dose in patients with CD70‐positive, metastatic RCC (mRCC). All subtypes of RCC were permitted, and no limit was set on the number of prior therapies. Safety assessments consisted of monitoring and recording all adverse events (AEs) and dose‐limiting toxicities (DLTs). Treatment response was assessed by radiographic tumor evaluation according to the Response Evaluation Criteria for Solid Tumors, version 1.1. A model‐based, modified continual‐reassessment method was used to estimate the probabilities of DLT and response. Results The maximum tolerated dose was determined to be 30 μg/kg, with thrombocytopenia as the DLT. The most common AEs were fatigue (67%), anemia (61%), and thrombocytopenia (56%). Of 18 enrolled patients, 1 achieved a partial response and 13 achieved stable disease, for a clinical benefit rate of 78%. Limitations of the study included the heavily pretreated nature of patients, receipt of a median of 4 prior lines of therapy (range, 1‐8 prior lines of therapy), and diminishing response potential. Conclusions The modest antitumor activity of SGN‐CD70A does not support its development in mRCC. However, given the high disease control rate in a heavily pretreated population and the modest toxicity profile, CD70 remains of interest because of its immunomodulatory properties.

New emerging targets in cancer immunotherapy: CD27 (TNFRSF7)

“…Furthermore, also CD70 targeting agents are tested in clinical trials with different compounds (table 1). 24 44 45 Here, CD70 is rather used as a specific target on the tumour cells.…”

“…SGN-CD70A was developed with a different cytotoxic agent, pyrrolobenzodiazepine, and investigated in n=18 CD70-positive RCC and n=20 patients with NHL in a phase I study (NCT02216890). One of 18 patients with RCC achieved a PR and 13/18 (72%) patients had a SD, resulting in a clinical benefit rate of 78% 44. In patients with NHL, 1/20 patients achieved a CR and 3/20 a PR 49.…”

“…Three patients had dose-limiting toxicities as in grade three nephrotic syndrome and Grade 4 neutropenia 21. In the therapy with SGN-CD70, thrombocytopenia occurring in 56% presented as dose-limiting toxicity 44. In the AMG 172 trial, the most common side effects were again thrombocytopenia (59%), nausea (54%), decreased appetite (49%), emesis (46%) and fatigue (35%) 45…”

Clinical relevance of CD70 expression in resected pancreatic cancer: Prognostic value and therapeutic potential

“…Furthermore, due to the lack of constitutive CD70 expression in normal tissues, CD70 may be an attractive therapeutic target [7,9]. Indeed, CD70-directed antibody has shown antitumor activity in vitro [9,12,19,20] and have demonstrated clinical responses against RCC and non-Hodgkin's lymphoma in clinical trials [21][22][23].…”

Clinical relevance of CD70 expression in resected pancreatic cancer: prognostic value and therapeutic potential

“…Recently, aberrant CD70 expression in cancer cells has been observed in several tumor types, including RCC [7,21], lymphocytic leukemia [11,19], ovarian carcinoma [8] [16], and breast cancer [14,15]. These ndings suggest that blocking CD70-related signals could be an appropriate therapeutic strategy for some tumors [9,19].…”