Multi-arm polymer conjugates of TLR agonist compounds and related immunotherapeutic treatment methods

A method of administration comprising administering to a subject having cancer (i) a conjugate comprising a Toll-like receptor (TLR) 7/8 activating amount of a TLR 7/8 agonist covalently attached, via a linkage-containing spacer moiety, to a multi-arm, water-soluble, non-peptidic polymer having a formula in accordance with

• Formula III:
• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
• L is —(CH2)m—, —(CH2)m—NH—C(O)—(CH2)m—, —CHF—(CH2)m—NH—C(O)—(CH2)m—, —CH(CH3)—NH—C(O)—(CH2)m—, —CH(CH(CH3)2)—NH—C(O)—(CH2)m—, —CH(CH2CH(CH3)2)—NH—C(O)—(CH2)m—, —C(CH3)2—NH—C(O)—(CH2)m—, a single bond, or —NH—(CH2)m—,
• each m is independently an integer from 1 to 5, inclusive;
• each n is independently an integer from 40 to 350, inclusive;
• R1 is hydrogen or —CH2—O—CH2—CH3;
• and
• R2 is hydrogen or hydroxyl, and (ii) am IL-2Rβ-activating amount of a long acting interleukin-2 receptor beta (IL-2Rβ)-biased agonist.

A combination for use in treating a subject having cancer, the combination comprising an IL-2Rβ-activating amount of a long acting IL-2Rβ-biased agonist and an innate immunity activating amount of a conjugate comprising a Toll-like Receptor (TLR) 7/8 agonist covalently attached, via a linkage-containing spacer moiety, to a multi-arm, water-soluble, non-peptidic polymer having a formula in accordance with Formula III:

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
• L is —(CH2)m—, —(CH2)m—NH—C(O)—(CH2)m—, —CHF—(CH2)m—NH—C(O)—(CH2)m—, —CH(CH3)—NH—C(O)—(CH2)m—, —CH(CH(CH3)2)—NH—C(O)—(CH2)m—, —CH(CH2CH(CH3)2)—NH—C(O)—(CH2)m—, —C(CH3)2—NH—C(O)—(CH2)m—, a single bond, or —NH—(CH2)m—,
• each m is independently an integer from 1 to 5, inclusive;
• each n is independently an integer from 40 to 350, inclusive;
• R1 is hydrogen or —CH2—O—CH2—CH3;
• and
• R2 is hydrogen or hydroxyl, accompanied by instructions for use in treating a subject having cancer.