Anti-PD-1 antibody alone or with low-dose decitabine and chemotherapy for relapsed or refractory cancers

Anti-PD-1 Antibody Alone or in Combination With Low-dose Decitabine and/or Chemotherapy in Relapsed or Refractory Malignancies: an Open-label Phase I/II Trial

This trial tests whether an anti-PD-1 immunotherapy given alone or with low-dose decitabine and chemotherapy can help people aged 12–75 whose cancers have come back or did not respond to prior treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 12 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT02961101 on ClinicalTrials.gov

What this trial studies

This phase 1/2 study administers an anti-PD-1 antibody every three weeks either alone or combined with low-dose decitabine and/or chemotherapy to patients with a variety of relapsed or refractory malignancies. The primary focus is feasibility and safety, with adverse events collected continuously during treatment and for 100 days after the last dose and graded by NCI CTCAE v4.0. Secondary and exploratory objectives include measuring antitumor activity (best overall response, objective response rate, progression-free and overall survival), characterizing immune effects, and searching for predictive biomarkers. Eligible participants must have measurable disease and prior therapies and will be treated and followed at the Biotherapeutic Department of Chinese PLA General Hospital in Beijing.

Who should consider this trial

Good fit: Ideal candidates are people aged 12–75 with histologically confirmed relapsed or refractory malignancies, measurable disease, ECOG performance status under 2, adequate organ function, and at least two prior chemotherapy regimens.

Not a fit: Patients with poor performance status (ECOG ≥2), significant organ dysfunction, rapidly progressing disease that prevents travel to Beijing, or cancers already controlled by standard therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, the regimen could shrink tumors or extend progression-free and overall survival for patients whose cancers have relapsed or are refractory to standard treatments.

How similar studies have performed: PD‑1 inhibitors have produced clear benefits in several cancers (for example Hodgkin lymphoma, lung cancer, and melanoma), and early-phase combinations with hypomethylating agents like decitabine have shown promising but still exploratory signals.

Eligibility criteria

Inclusion Criteria:

1. Subjects must have histological confirmation of relapsed or refractory malignancies,including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.
2. 12 to 75 years of age.
3. ECOG performance of less than 2.
4. Life expectancy of at least 3 months.
5. Subjects with lymphoma must have at least one measureable lesion \>1 cm as defined by lymphoma response criteria; with solid tumors must have at least one measureable lesion \>1 cm per RECIST1.1.
6. Subjects must have received at least two prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.
7. Subjects must have adequate bone marrow, live, renal, lung and heart functions.

   1. Absolute neutrophil count greater than or equal to 1,000/μL.
   2. Platelet count greater than or equal to 70,000/µL.
   3. Serum bilirubin level less than or equal to 1.5 x upper limits of normal (ULN).
   4. Serum creatinine less than or equal to 1.5 x ULN.
   5. Alanine aminotransferase \[ALT or SGPT\] and aspartate aminotransferase \[AST or SGOT\] less than or equal to 2.5 x ULN.

Exclusion Criteria:

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary and intestinal infection especially.
3. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .
4. Prior organ allograft.
5. Women who are pregnant or breastfeeding.
6. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Where this trial is running

Beijing, Beijing Municipality

• Biotherapeutic Department of Chinese PLA General Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Yan Zhang, Doctor — Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
• Study coordinator: Weidong Han, doctor

Conditions Malignancies Multiple; relapsed or refractory; malignancies; decitabine; anti-PD-1 antibody; chemotherapy