run-genkey is working fine in my test environment as well.

Thank you for your response! I tried out all variants of gpgme_pinentry_mode_t and implemented a passphrase callback (using gpgme_set_passphrase_cb as suggested). It turns out that the callback is not invoked at all. However, if I switch back to gnupg 2.2.27, the callback is being invoked and the key is being generated (using the passphrase specified by the callback, as expected).