Protein-polymer-drug conjugates and methods of using same

A method of alleviating a symptom of a cancer in a subject in need thereof, wherein the subject is identified as having low HER2 expression, comprising administering a conjugate to the subject in an amount sufficient to alleviate the symptom of the cancer, wherein the conjugate is of Formula (Ie), comprising a polymeric scaffold comprising a poly(1-hydroxymethylethylene hydroxymethyl-formal) (PHF):

• wherein:
• the PHF has a molecular weight ranging from about 2 kDa to about 40 kDa;
• PBRM is trastuzumab or a biosimilar thereof;
• each occurrence of D independently is a therapeutic agent having a molecular weight of ≦5kDa, and the
• the between D and the carbonyl group denotes direct or indirect attachment of D to the carbonyl group,
• X is CH2, O, or NH;
• one of Xa and Xb is H and the other is a water-soluble maleimido blocking moiety, or Xaand Xb, together with the carbon atoms to which they are attached for a carbon-carbon double bond,
• m1 is an integer from 1 to about 140,
• m7 is an integer from 1 to about 40, wherein the sum of m1 and m7 is about 2 to about 180,
• m is an integer from 1 to about 300,
• m3a is an integer from 0 to about 17,
• m3b is an integer from 1 to about 8, wherein the sum of m3a and m3b is an integer between 1 and about 18,
• the sum of m, m1, m7, m3a, and m3b ranges from about 15 to about 300, and
• m5is an integer from 1 to about 10.