Clinical methods for use of a PD-L1-binding molecule comprising a Shiga toxin effector

Patent metadata

Field	Value
Publication number	US-12180284-B2
Application number	US-202117553333-A
Country	US
Kind code	B2
Filing date	Dec 16, 2021
Priority date	Dec 16, 2020
Publication date	Dec 31, 2024
Grant date	Dec 31, 2024

Abstract

The present disclosure relates to PD-L1-binding molecules comprising a Shiga toxin effector region, a PD-L1-binding region, and a T cell epitope, and pharmaceutical compositions thereof. The PD-L1 binding molecules and pharmaceutical compositions thereof have uses for selectively killing specific cells (e.g., PD-L1 positive tumor cells and/or immune cells), for selectively delivering cargos to specific cells (e.g., PD-L1 positive tumor cells or immune cells), and as therapeutics for treating or slowing the progression of cancer (e.g., non-small cell lung cancer or squamous cell carcinoma of the head and neck). The present disclosure also relates to clinical methods for use of the disclosed PD-L1 binding molecules for treating a subject in need thereof.

First claim

What is claimed is:

1. A method for treating or slowing the progression of a solid tumor, the method comprising administering to a subject in need thereof an effective amount of a PD-L1 binding molecule, wherein the PD-L1 binding molecule comprises a polypeptide having the sequence of SEQ ID NO: 1;
wherein the PD-L1 binding molecule is administered at a dose of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg 1 μg/kg to about 200 μg/kg of the subject's body weight.

2. The method of claim 1 , wherein the solid tumor expresses PD-L1.

3. The method of claim 1 , wherein the PD-L1 binding molecule is administered weekly during a first 28-day cycle, wherein the PD-L1 binding molecule is administered on days 1, 8, 15, and 22 of the first 28-day cycle.

4. The method of claim 1 , wherein the PD-L1 binding molecule is administered two times during a first 28-day cycle, wherein the PD-L1 binding molecule is administered on days 1 and 15 of the first 28-day cycle.

5. The method of claim 1 , wherein the PD-L1 binding molecule is administered three times during a first 28-day cycle, wherein the PD-L1 binding molecule is administered on days 1, 8, and 15 of the first 28-day cycle.

6. The method of claim 3 , further comprising administering the PD-L1 binding molecule weekly during a second 28-day cycle following the first 28-day cycle, wherein the PD-L1 binding molecule is administered on days 1, 8, 15, and 22 of the second 28-day cycle.

7. The method of claim 3 , wherein the PD-L1 binding molecule is administered two times during a second 28-day cycle following the first 28-day cycle, wherein the PD-L1 binding molecule is administered on days 1 and 15 of the second 28-day cycle.

8. The method of claim 3 , wherein the PD-L1 binding molecule is administered three times during a second 28-day cycle, wherein the PD-L1 binding molecule is administered on days 1, 8, and 15 of the second 28-day cycle.

9. The method of claim 6 , wherein the PD-L1 binding molecule is administered at a dose of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg, about 90 μg/kg, about 95 μg/kg, about 100 μg/kg, about 125 #g/kg, or about 150 μg/kg of the subject's body weight during the second 28-day cycle.

10. The method of claim 6 , further comprising administering the PD-L1 binding molecule weekly during a third 28-day cycle following the first and second 28-day cycles, wherein the PD-L1 binding molecule is administered on days 1, 8, 15, and 22 of the third 28-day cycle.

11. The method of claim 6 , wherein the PD-L1 binding molecule is administered two times during a third 28-day cycle following the first and second 28-day cycles, wherein the PD-L1 binding molecule is administered on days 1 and 15 of the third 28-day cycle.

12. The method of claim 6 , wherein the PD-L1 binding molecule is administered three times during a third 28-day cycle following the first and second 28-day cycles, wherein the PD-L1 binding molecule is administered on days 1, 8, and 15 of the third 28-day cycle.

13. The method of claim 10 , wherein the PD-L1 binding molecule is administered at a dose of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg of the subject's body weight during the third 28-day cycle.

14. The method of claim 10 , further comprising administering the PD-L1 binding molecule for at least one additional 28-day cycle.

15. The method of claim 14 , wherein the PD-L1 binding molecule is administered at a dose of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg of the subject's body weight during the at least one additional 28-day cycle.

16. The method of claim 3 , wherein the dose of the PD-L1 binding molecule administered to the subject over one or more cycles is about 5 mg to about 100 mg.

17. The method of claim 3 , wherein the PD-L1 binding molecule is administered by intravenous infusion.

18. The method of claim 17 , wherein the intravenous infusion is over about 5 minutes to about 120 minutes.

19. The method of claim 18 , wherein the intravenous infusion is over about 30 minutes.

20. The method of claim 1 , wherein the solid tumor is squamous cell carcinoma of the head and neck.

21. The method of claim 1 , wherein the solid tumor is non-small cell lung cancer.

22. The method of claim 1 , wherein the solid tumor is unresectable, locally advanced, or metastatic.

23. The method of claim 1 , wherein the cancer is relapsed or refractory to treatment with at least one additional anti-cancer therapy.

24. The method of claim 23 , wherein the cancer is relapsed or refractory to treatment with at least one of ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, tremelimumab or cemiplimab.

25. The method of claim 23 , wherein the cancer is relapsed or refractory to a platinum-based therapy.

26. A method for treating or slowing the progression of non-small cell lung cancer, the method comprising administering to a subject in need thereof an effective amount of a PD-L1 binding molecule, wherein the PD-L1 binding molecule comprises a polypeptide having the sequence of SEQ ID NO: 1;
wherein the PD-L1 binding molecule is administered at a dose in the range of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg of the subject's body weight.

27. The method of claim 26 , wherein the non-small cell lung cancer expresses PD-L1.

28. A method for treating or slowing the progression of squamous cell carcinoma of the head and neck, the method comprising administering to a subject in need thereof an effective amount of a PD-L1 binding molecule, wherein the PD-L1 binding molecule comprises a polypeptide having the sequence of SEQ ID NO: 1;
wherein the PD-L1 binding molecule is administered at a dose in the range of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg of the subject's body weight.

29. The method of claim 28 , wherein the squamous cell carcinoma of the head and neck expresses PD-L1.

30. A method for treating or slowing the progression of a solid tumor that expresses PD-L1, the method comprising administering to a subject in need thereof an effective amount of a PD-L1 binding molecule, wherein the PD-L1 binding molecule comprises a polypeptide having the sequence of SEQ ID NO: 1;
wherein the PD-L1 binding molecule is administered at a dose in the range of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg of the subject's body weight.

31. A method of treating or slowing the progression of a solid tumor that expresses PD-L1, the method comprising screening the subject for an HLA: A*02 haplotype and treating the subject that is positive for the HLA: A*02 haplotype with a PD-L1 binding molecule comprising a polypeptide having the sequence of SEQ ID NO: 1;
wherein the PD-L1 binding molecule is administered at a dose in the range of about 50 μg/kg, about 63 μg/kg, about 75 μg/kg, about 80 μg/kg, or about 85 μg/kg of the subject's body weight.

32. A method of treating or slowing the progression of a solid tumor, wherein the method comprises administering to a subject in need thereof an effective amount of a PD-L1 binding molecule, wherein the PD-L1 binding molecule comprises a polypeptide having the sequence of SEQ

Assignees

• Molecular Templates Inc

Inventors

• Poma Eric
• Willert Erin
• Ramos Hilario
• Liu Jensing
• Waltzman Roger

Classifications

• G01N33/5752

  of the lungs · CPC title

• A61K39/0011

  Cancer antigens · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title