Article Text

Download PDFPDF

Tumor response from durvalumab (MEDI4736) + tremelimumab treatment in patients with advanced non-small cell lung cancer (NSCLC) is observed regardless of PD-L1 status
  1. Naiyer Rizvi1,
  2. Jamie Chaft2,
  3. Ani Balmanoukian3,
  4. Sarah B Goldberg4,
  5. Rachel E Sanborn5,
  6. Keith E Steele6,
  7. Marlon C Rebelatto6,
  8. Yu Gu6,
  9. Joyson J Karakunnel6 and
  10. Scott Antonia7
  1. Aff1 grid.239585.00000000122852675Columbia University Medical Center New York NY USA
  2. Aff2 grid.51462.340000000121719952Memorial Sloan Kettering Cancer Center New York NY USA
  3. Aff3 grid.488730.0The Angeles Clinic and Research Institute Los Angeles CA USA
  4. Aff4 grid.433818.5Yale University, Yale Cancer Center New Haven CT USA
  5. Aff5 grid.415337.7Earle A. Chiles Research InstituteProvidence Cancer Center Portland OR USA
  6. Aff6 grid.418152.bMedImmune Gaithersburg MD USA
  7. Aff7 grid.170693.a000000012353285XMoffitt Cancer Center Tampa FL USA

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Meeting abstracts


As single agents, durvalumab (MEDI4736), a human IgG1 anti-PD-L1 antibody, and tremelimumab, a human IgG2 anti-CTLA-4 antibody, have shown acceptable safety profiles and antitumor activity. Similar to other anti-PD-L1/anti-PD-1 monotherapies, durvalumab has shown greater objective tumor response rates in PD-L1-positive patients compared with PD-L1-negative patients. Anti-CTLA4 therapies activate T-cells and may increase immune infiltrate and PD-L1 expression in tumor cells and tumor infiltrating immune cells. Thus, combination therapy with durvalumab and tremelimumab could be active in NSCLC regardless of baseline PD-L1 expression.


This is a phase 1, open-label, dose-escalation/expansion study (NCT02000947) of D+T in patients with Stage III/IV NSCLC (any number of prior lines of therapy; immunotherapy-naïve). The primary endpoint is safety and tolerability; secondary endpoints include investigator-reported RECIST v1.1 response. PD-L1 expression was tested retrospectively using an immunohistochemical assay (Ventana).


As of 1 June 2015, 102 patients received treatment in the dose escalation phase; combinations of durvalumab [3 mg/kg (D3) to 20 mg/kg (D20) every 2 (q2w) or 4 weeks (q4w)] and tremelimumab [1 mg/kg (T1) to 3 mg/kg (T3)] q4w, plus a D15 + T10 combination, were explored. Across all cohorts, 80% and 42% of patients had ≥1 treatment-related AE (any Grade and Grade 3/4, respectively); 28% discontinued treatment due to a related AE. A greater frequency of AEs, without a corresponding increase in tumor response, was seen with increasing T dose. In the combined T1 cohort (D10–D20), 73% and 30% of patients had ≥1 related AE (any Grade and Grade 3/4, respectively); 16% discontinued treatment due to a related AE. There were 3 treatment-related deaths (myasthenia gravis, T1; pericardial effusion, T1; neuromuscular disorder, T3).

84 patients (73 EGFR/ALK wild-type; 77 non-squamous; 48 with ≥2 prior lines of therapy) were evaluable for response (Table 1). The overall response rate (confirmed+unconfirmed) was 25%. Higher response rates were observed in those with 1 vs ≥2 prior therapies. Response rates do not appear dependent on PD-L1 status: 35% (PD-L1-positive), 22% (PD-L1-negative, <25% tumor cell staining) and 33% (PD-L1-negative, 0% tumor cell staining). Similar findings were observed for the combined T1 cohort. D+T also showed good durability of response similar to that seen for monotherapy.

Response rates (Confirmed/unconfirmed with ≥16 weeks follow-up)


D+T at selected phase 3 dose (D20, T1) has a manageable tolerability profile and anti-tumor activity in NSCLC. Unlike anti- PD-1/PD-L1 monotherapies, the combination of D+T appears to be active regardless of PD-L1 status, including even in patients with no tumor cell membrane PD-L1 staining, a setting where patients would not be expected to derive significant benefit from anti-PD-1/PD-L1 monotherapy over current standard of care [1, 2].


  1. 1.
  2. 2.