Clin Cancer Res: AZD4635 is well tolerated in solid tumors as monotherapy or in combination with duvalumab

The safety of AZD4635 monotherapy or in combination with duvalumab in solid tumors is unclear
.

A study from Clin Cancer Res showed that AZD4635 was well
tolerated in solid tumors as monotherapy or in combination with duvalumab.

▎Research protocol:

This is a phase I/b, open-label, multicenter study
.
In phase I.
a (dose escalation phase), the trial subjects were patients with relapsed/refractory solid tumors; In phase I.
b (dose expansion phase), subjects were patients with metastatic castration-resistant prostate cancer (mCRPC) or colorectal cancer who had not previously been treated with checkpoint inhibitors, non-small cell lung cancer that had previously been treated with anti-PD-1/PD-L1, or other solid tumors (previously not treated with checkpoint inhibitors or previously treated with anti-PD-1/PD-L1
).
。 Enrolled patients will receive AZD4635 monotherapy (75-200 mg once daily or 125 mg twice daily) or in combination with duvalumab (AZD4635 at a dose of 75 or 100 mg once daily).

The main objective of this study is the safety of treatment; Secondary objectives include antitumor activity and pharmacokinetics; Exploratory goals include the evaluation
of adenosine gene tags in patients with mCRPC.

▎Key findings:

(1) As of September 8, 2020, a total of 250 patients have been treated (AZD4635, n=161; AZD4635 + duvalumab, n=89).

(2) During phase I.
a of the trial, dose-limiting toxicities (DLTs) were observed in 2 and 1 person in patients treated with monotherapy (125 mg twice daily) and combination therapy (75 mg)
by nanosuspension, respectively.
The most common treatment-related adverse events included nausea, fatigue, vomiting, decreased appetite, dizziness, and diarrhoea
.

(3) The recommended dose (RP2D) of the phase II trial of AZD4635 capsule preparation is 75mg, once a day, for monotherapy or in combination with duvalumab
.

(4) The pharmacokinetic profile of AZD4635 is proportional to the dose, in addition, the exposure of a nanosuspension of a nanosuspension or a capsule formulation of 75 mg at a once-daily dose is sufficient to reach the target
.

(5) Tumor response (2/39 and 6/37 people, respectively) and prostate-specific antigen reaction (3/60 and 10/45 people, respectively) can be observed in mCRPC patients undergoing monotherapy or combination therapy.

The median progression-free survival (PFS) for patients based on high and low blood adenosine gene tags was 21 weeks and 8.
7 weeks
, respectively.

▎Outlook:

AZD4635 is well
tolerated as monotherapy or in combination with duvalumab.
The results that the treatment can achieve the target response support the further phase II joint study
in the mCRPC patient population.