It's not as difficult as it looks. For elastic ##2 \rightarrow 2## scattering of particles of the same mass, ##m## we have with ##p_1,p_2## being the four-momenta in the initial and ##p_3,p_4## those of the final state
$$s=(p_1+p_2)^2=(p_3+p_4)^2, \quad t=(p_1-p_3)^2=(p_2-p_4)^2, \quad u=(p_1-p_4)^2=(p_2-p_3)^2.$$
Then we have the on-shell conditions ##p_1^2=p_2^2=p_3^2=p_4^2=m^2##.
Now let's specialize to the CM frame, where ##\vec{p}_2=-\vec{p}_1=-\vec{p}## and ##\vec{p}_4=-\vec{p}_3=-\vec{p}'##. In this frame we have
$$s=(E_1+E_2)^2=4 E_1^2=4 E_3^2 \; \Rightarrow \; |\vec{p}'|=|\vec{p}|$$
and
$$s=4(m^2+\vec{p}^2) \; \Rightarrow \; |\vec{p}|=|\vec{p}'|=\frac{1}{2} \sqrt{s-4m^2}.$$
The only other parameter of the scattering in the CM frame is the scattering angle ##\vartheta##, defined by
$$\vec{p} \cdot \vec{p}'=|\vec{p}|^2 \cos \vartheta.$$
This angle must be related to the Mandelstam variable ##t## (or ##u##, but ##s+t+u=4m^2##).Indeed we have
$$t=(p_1-p_3)^2=2 m^2-2 p_1 \cdot p_3=2m^2-2(E_1 E_3-\vec{p} \cdot \vec{p}')=2 (m^2-E_1^2+|\vec{p}|^2 \cos \vartheta) = -2 |\vec{p}|^2 (1-\cos \vartheta)=-\sqrt{s-4m^2} (1-\cos \vartheta).$$
The manifestly covariant form of the differential cross section, expressed in Mandelstam variables only reads
$$\frac{\mathrm{d} \sigma}{\mathrm{d} t}=\frac{1}{64 \pi s |\vec{p}|^2} \mathcal{M}(s,t).$$
For the more general case of ##2 \rightarrow 2## scattering (and more kinematics), see
http://pdg.lbl.gov/2016/reviews/rpp2016-rev-kinematics.pdf