To formulate a thesis in response to this question, we must first understand what Marx meant by "alienation." For Marx, alienation was a multi-faceted phenomenon that occurred as a result of the rise of industrial capitalism. He thought that capitalism alienated people from their work in that wage workers did not receive compensation for the true value of their labor. He also argued that capitalism, because it reduced people to the value they could provide as workers, alienated people from their humanity. It severed the relationships—family in particular—that made people human.
Gregor Samsa, the protagonist of Metamorphosis, embodies this alienation. Such alienation was a frequent theme of intellectual life in the early twentieth century. On the one hand, Gregor's alienation takes a blatant, tangible form. He literally becomes less than human when he is transformed into a bug.
As the story goes on, it is revealed that this is only a physical manifestation of feelings Gregor already had. He hates his job as a salesman, particularly lamenting the fact that it affords him few opportunities for meaningful human contact. Shortly after he comes to the grim realization that he has been transformed, he lies in bed thinking about his work life:
"Oh, God", he thought, "what a strenuous career it is that I've chosen! Travelling day in and day out. Doing business like this takes much more effort than doing your own business at home, and on top of that there's the curse of travelling, worries about making train connections, bad and irregular food, contact with different people all the time so that you can never get to know anyone or become friendly with them. It can all go to Hell!"
As the plot continues, it becomes clear that Gregor lives in a world that views him only in terms of his labor and his earning potential. Though he had never previously missed a day of work in many years working for his company, his supervisors threaten to fire him before they even realize what has happened.
Later, it emerges that Gregor's father's business has failed, and that only Gregor's income is keeping the family afloat. Once he is transformed and can no longer provide the income his family needs, they abandon him and turn to his sister Grete for support. In short, the incident is the ultimate example of one man's alienation from society, both in a Marxist and a broader sense. Since the question requires engaging with Marx's theory of alienation, it makes sense to stress the ways that Gregor's economic role in society and within his family supersedes his humanity. This loss of humanity is manifested and revealed by his metamorphosis.