deltatrials
Active Not Recruiting PHASE1 INTERVENTIONAL 1-arm NCT02298959

Testing the PD-1 Antibody, MK3475, Given With Ziv-aflibercept in Patients With Advanced Cancer

A Phase 1 Trial of MK-3475 Plus Ziv-Aflibercept in Patients With Advanced Solid Tumors

Sponsor: National Cancer Institute (NCI)

Conditions Clinical Stage IV Cutaneous Melanoma AJCC v8 Metastatic Colorectal Carcinoma Metastatic Malignant Solid Neoplasm Metastatic Melanoma Metastatic Ovarian Carcinoma Metastatic Renal Cell Carcinoma Platinum-Resistant Ovarian Carcinoma Recurrent Melanoma Recurrent Renal Cell Carcinoma Refractory Melanoma Refractory Renal Cell Carcinoma Sarcoma Stage IV Colorectal Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Stage IV Renal Cell Cancer AJCC v8
Interventions Biopsy Procedure Biospecimen Collection Computed Tomography Magnetic Resonance Elastography Pembrolizumab Ziv-Aflibercept
Updated 63 times since 2017 Last updated: Mar 12, 2026 Started: Apr 8, 2015 Primary completion: May 21, 2025 Completion: Jan 20, 2027
This information is for research purposes only and is not medical advice. Consult a healthcare provider before making any medical decision.

Listed as NCT02298959, this PHASE1 trial focuses on Clinical Stage IV Cutaneous Melanoma AJCC v8 and Metastatic Colorectal Carcinoma and remains ongoing. Sponsored by National Cancer Institute (NCI), it has been updated 63 times since 2015, reflecting substantial change activity. This study contributes to the evolving evidence base for cancer treatment protocols.

Study Description(click to expand)

PRIMARY OBJECTIVE: I. To determine the safety, tolerability and recommended phase II dosing for the combination of ziv-aflibercept plus MK-3475 (pembrolizumab) in patients with unresectable stage III or stage IV melanoma, renal cell cancer, ovarian cancer, colorectal cancer, or sarcoma. SECONDARY OBJECTIVES: I. To obtain preliminary estimates of progression-free survival at 6 months. II. To obtain preliminary estimates of the rate of 1-year overall survival. III. To obtain preliminary estimates of the response rate. IV. To obtain preliminary estimates of time to progression. V. To perform correlative sciences that provide information regarding the mechanisms of action for this combination treatment. OUTLINE: This is a dose-escalation and dose expansion study of ziv-aflibercept. Patients receive pembrolizumab intravenously (IV) over approximately 30 minutes and ziv-aflibercept IV over 1-2 hours on day 1. Cycles repeat every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), blood sample collection and tumor biopsy throughout the study. After completion of study treatment, patients are followed up for at least 12 weeks.

PRIMARY OBJECTIVE:

I. To determine the safety, tolerability and recommended phase II dosing for the combination of ziv-aflibercept plus MK-3475 (pembrolizumab) in patients with unresectable stage III or stage IV melanoma, renal cell cancer, ovarian cancer, colorectal cancer, or sarcoma.

SECONDARY OBJECTIVES:

I. To obtain preliminary estimates of progression-free survival at 6 months. II. To obtain preliminary estimates of the rate of 1-year overall survival. III. To obtain preliminary estimates of the response rate. IV. To obtain preliminary estimates of time to progression. V. To perform correlative sciences that provide information regarding the mechanisms of action for this combination treatment.

OUTLINE: This is a dose-escalation and dose expansion study of ziv-aflibercept.

Patients receive pembrolizumab intravenously (IV) over approximately 30 minutes and ziv-aflibercept IV over 1-2 hours on day 1. Cycles repeat every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), blood sample collection and tumor biopsy throughout the study.

After completion of study treatment, patients are followed up for at least 12 weeks.

Status Flow

~Jan 2017 – ~Feb 2017 · 31 days · monthly snapshot~Feb 2017 – ~Jun 2017 · 4 months · monthly snapshot~Jun 2017 – ~Aug 2017 · 2 months · monthly snapshot~Aug 2017 – ~Dec 2017 · 4 months · monthly snapshot~Dec 2017 – ~Mar 2018 · 3 months · monthly snapshot~Mar 2018 – ~Jun 2018 · 3 months · monthly snapshot~Jun 2018 – ~Aug 2018 · 2 months · monthly snapshot~Aug 2018 – ~Oct 2018 · 2 months · monthly snapshot~Oct 2018 – ~Nov 2018 · 31 days · monthly snapshot~Nov 2018 – ~Dec 2018 · 30 days · monthly snapshot~Dec 2018 – ~Jan 2019 · 31 days · monthly snapshot~Jan 2019 – ~Mar 2019 · 59 days · monthly snapshot~Mar 2019 – ~Apr 2019 · 31 days · monthly snapshot~Apr 2019 – ~May 2019 · 30 days · monthly snapshot~May 2019 – ~Aug 2019 · 3 months · monthly snapshot~Aug 2019 – ~Oct 2019 · 2 months · monthly snapshot~Oct 2019 – ~Nov 2019 · 31 days · monthly snapshot~Nov 2019 – ~Jan 2020 · 2 months · monthly snapshot~Jan 2020 – ~Feb 2020 · 31 days · monthly snapshot~Feb 2020 – ~Mar 2020 · 29 days · monthly snapshot~Mar 2020 – ~Apr 2020 · 31 days · monthly snapshot~Apr 2020 – ~May 2020 · 30 days · monthly snapshot~May 2020 – ~Jun 2020 · 31 days · monthly snapshot~Jun 2020 – ~Jul 2020 · 30 days · monthly snapshot~Jul 2020 – ~Nov 2020 · 4 months · monthly snapshot~Nov 2020 – ~Jan 2021 · 2 months · monthly snapshot~Jan 2021 – ~Feb 2021 · 31 days · monthly snapshot~Feb 2021 – ~Apr 2021 · 59 days · monthly snapshot~Apr 2021 – ~Jun 2021 · 2 months · monthly snapshot~Jun 2021 – ~Sep 2021 · 3 months · monthly snapshot~Sep 2021 – ~Oct 2021 · 30 days · monthly snapshot~Oct 2021 – ~Dec 2021 · 2 months · monthly snapshot~Dec 2021 – ~Jan 2022 · 31 days · monthly snapshot~Jan 2022 – ~Feb 2022 · 31 days · monthly snapshot~Feb 2022 – ~Apr 2022 · 59 days · monthly snapshot~Apr 2022 – ~May 2022 · 30 days · monthly snapshot~May 2022 – ~Jul 2022 · 2 months · monthly snapshot~Jul 2022 – ~Sep 2022 · 2 months · monthly snapshot~Sep 2022 – ~Dec 2022 · 3 months · monthly snapshot~Dec 2022 – ~Feb 2023 · 2 months · monthly snapshot~Feb 2023 – ~May 2023 · 3 months · monthly snapshot~May 2023 – ~Sep 2023 · 4 months · monthly snapshot~Sep 2023 – ~Oct 2023 · 30 days · monthly snapshot~Oct 2023 – ~Dec 2023 · 2 months · monthly snapshot~Dec 2023 – ~Jan 2024 · 31 days · monthly snapshot~Jan 2024 – ~Feb 2024 · 31 days · monthly snapshot~Feb 2024 – ~Apr 2024 · 2 months · monthly snapshot~Apr 2024 – ~Jun 2024 · 2 months · monthly snapshot~Jun 2024 – ~Jul 2024 · 30 days · monthly snapshot~Jul 2024 – ~Aug 2024 · 31 days · monthly snapshot~Aug 2024 – ~Sep 2024 · 31 days · monthly snapshot~Sep 2024 – ~Dec 2024 · 3 months · monthly snapshot~Dec 2024 – ~Jan 2025 · 31 days · monthly snapshot~Jan 2025 – ~May 2025 · 4 months · monthly snapshot~May 2025 – ~Jun 2025 · 31 days · monthly snapshot~Jun 2025 – ~Oct 2025 · 4 months · monthly snapshot~Oct 2025 – ~Dec 2025 · 2 months · monthly snapshot~Dec 2025 – ~Feb 2026 · 2 months · monthly snapshot~Jan 2026 – present · 3 months · monthly snapshot~Feb 2026 – ~Mar 2026 · 28 days · monthly snapshot~Feb 2026 – present · 2 months · monthly snapshot~Mar 2026 – present · 40 days · monthly snapshot~Mar 2026 – present · 40 days · monthly snapshot

Change History

63 versions recorded

  1. Mar 2026 — Present [monthly]

    Active Not Recruiting PHASE1

  2. Mar 2026 — Present [monthly]

    Active Not Recruiting PHASE1

  3. Feb 2026 — Mar 2026 [monthly]

    Active Not Recruiting PHASE1

  4. Feb 2026 — Present [monthly]

    Active Not Recruiting PHASE1

  5. Jan 2026 — Present [monthly]

    Active Not Recruiting PHASE1

▶ Show 58 earlier versions

  1. Dec 2025 — Feb 2026 [monthly]

    Active Not Recruiting PHASE1

  2. Oct 2025 — Dec 2025 [monthly]

    Active Not Recruiting PHASE1

  3. Jun 2025 — Oct 2025 [monthly]

    Active Not Recruiting PHASE1

  4. May 2025 — Jun 2025 [monthly]

    Active Not Recruiting PHASE1

  5. Jan 2025 — May 2025 [monthly]

    Active Not Recruiting PHASE1

  6. Dec 2024 — Jan 2025 [monthly]

    Active Not Recruiting PHASE1

  7. Sep 2024 — Dec 2024 [monthly]

    Active Not Recruiting PHASE1

  8. Aug 2024 — Sep 2024 [monthly]

    Active Not Recruiting PHASE1

  9. Jul 2024 — Aug 2024 [monthly]

    Active Not Recruiting PHASE1

  10. Jun 2024 — Jul 2024 [monthly]

    Active Not Recruiting PHASE1

  11. Apr 2024 — Jun 2024 [monthly]

    Active Not Recruiting PHASE1

  12. Feb 2024 — Apr 2024 [monthly]

    Active Not Recruiting PHASE1

  13. Jan 2024 — Feb 2024 [monthly]

    Active Not Recruiting PHASE1

  14. Dec 2023 — Jan 2024 [monthly]

    Active Not Recruiting PHASE1

  15. Oct 2023 — Dec 2023 [monthly]

    Active Not Recruiting PHASE1

  16. Sep 2023 — Oct 2023 [monthly]

    Active Not Recruiting PHASE1

  17. May 2023 — Sep 2023 [monthly]

    Active Not Recruiting PHASE1

  18. Feb 2023 — May 2023 [monthly]

    Active Not Recruiting PHASE1

  19. Dec 2022 — Feb 2023 [monthly]

    Active Not Recruiting PHASE1

  20. Sep 2022 — Dec 2022 [monthly]

    Active Not Recruiting PHASE1

    Status: Recruiting → Active Not Recruiting

  21. Jul 2022 — Sep 2022 [monthly]

    Recruiting PHASE1

  22. May 2022 — Jul 2022 [monthly]

    Recruiting PHASE1

  23. Apr 2022 — May 2022 [monthly]

    Recruiting PHASE1

  24. Feb 2022 — Apr 2022 [monthly]

    Recruiting PHASE1

  25. Jan 2022 — Feb 2022 [monthly]

    Recruiting PHASE1

  26. Dec 2021 — Jan 2022 [monthly]

    Recruiting PHASE1

  27. Oct 2021 — Dec 2021 [monthly]

    Recruiting PHASE1

  28. Sep 2021 — Oct 2021 [monthly]

    Recruiting PHASE1

  29. Jun 2021 — Sep 2021 [monthly]

    Recruiting PHASE1

  30. Apr 2021 — Jun 2021 [monthly]

    Recruiting PHASE1

  31. Feb 2021 — Apr 2021 [monthly]

    Recruiting PHASE1

  32. Jan 2021 — Feb 2021 [monthly]

    Recruiting PHASE1

  33. Nov 2020 — Jan 2021 [monthly]

    Recruiting PHASE1

  34. Jul 2020 — Nov 2020 [monthly]

    Recruiting PHASE1

  35. Jun 2020 — Jul 2020 [monthly]

    Recruiting PHASE1

  36. May 2020 — Jun 2020 [monthly]

    Recruiting PHASE1

  37. Apr 2020 — May 2020 [monthly]

    Recruiting PHASE1

  38. Mar 2020 — Apr 2020 [monthly]

    Recruiting PHASE1

  39. Feb 2020 — Mar 2020 [monthly]

    Recruiting PHASE1

  40. Jan 2020 — Feb 2020 [monthly]

    Recruiting PHASE1

  41. Nov 2019 — Jan 2020 [monthly]

    Recruiting PHASE1

  42. Oct 2019 — Nov 2019 [monthly]

    Recruiting PHASE1

  43. Aug 2019 — Oct 2019 [monthly]

    Recruiting PHASE1

  44. May 2019 — Aug 2019 [monthly]

    Recruiting PHASE1

  45. Apr 2019 — May 2019 [monthly]

    Recruiting PHASE1

  46. Mar 2019 — Apr 2019 [monthly]

    Recruiting PHASE1

  47. Jan 2019 — Mar 2019 [monthly]

    Recruiting PHASE1

  48. Dec 2018 — Jan 2019 [monthly]

    Recruiting PHASE1

    Status: Suspended → Recruiting

  49. Nov 2018 — Dec 2018 [monthly]

    Suspended PHASE1

  50. Oct 2018 — Nov 2018 [monthly]

    Suspended PHASE1

  51. Aug 2018 — Oct 2018 [monthly]

    Suspended PHASE1

  52. Jun 2018 — Aug 2018 [monthly]

    Suspended PHASE1

  53. Mar 2018 — Jun 2018 [monthly]

    Suspended PHASE1

    Status: Recruiting → Suspended

  54. Dec 2017 — Mar 2018 [monthly]

    Recruiting PHASE1

  55. Aug 2017 — Dec 2017 [monthly]

    Recruiting PHASE1

  56. Jun 2017 — Aug 2017 [monthly]

    Recruiting PHASE1

  57. Feb 2017 — Jun 2017 [monthly]

    Recruiting PHASE1

  58. Jan 2017 — Feb 2017 [monthly]

    Recruiting PHASE1

    First recorded

Apr 2015

Trial started

Per CT.gov start date — pre-dates our first snapshot

Eligibility Summary

No eligibility information available.

Contact Information

Sponsor contact:
  • National Cancer Institute (NCI)
Data source: National Cancer Institute (NCI)

For direct contact, visit the study record on ClinicalTrials.gov .

Study Locations