NCT03527251: SEQUENCE

Anti-CTLA-4 Antibody Followed by Anti-PD-1 Antibody in Recurrent or Metastatic NSCLC

Status unknown Phase 1 Last updated 30 May 2018

What this trial tests

Phase 1 trial testing Ipilimumab in Non Small Cell Lung Cancer in 10 participants. Status unknown.

Timeline

15 May 2018

Primary endpoint
31 December 2018

31 December 2019

Quick facts

Lead sponsor	Sun Yat-sen University
Phase	Phase 1
Status	Status unknown
Study type	INTERVENTIONAL
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	15 May 2018
Primary completion	31 December 2018
Estimated completion	31 December 2019
Sites	1 location across China

Drugs / interventions tested

• Ipilimumab — full drug profile →
• SHR-1210 — full drug profile →

Conditions studied

• Non Small Cell Lung Cancer — all drugs for Non Small Cell Lung Cancer →

Sponsor

Sun Yat-sen University

Who can join

18 and older, any sex, with Non Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Immunotherapy has made rapid progress in melanoma, Hodgkin's lymphoma, non-small cell lung cancer, and bladder cancer, etc. Preclinical data suggested that the use of anti-PD-1 antibody in combination with CTLA-4 receptor blockers may increase antitumor activity. The CheckMate-012 study showed that nivolumab and ipilimumab combination therapy achieved an overall response rate of 43% in unselected patients with non-small cell lung cancer, compared with 23% in the nivolumab monotherapy group; and in the PD-L1 positive subgroup, nivolumab in combination with ipilimumab showed a response rate of 57%, while nivolumab alone was 28%. This showed that the combination therapy of nivolumab and ipilimumab can increase the efficacy, but the adverse events of grade 3 or above of combination therapy reach 37%. The toxic side effects limit the widespread use of nivolumab in combination with ipilimumab therapy.

However, since the action of ipilimumab is limited to the initiation of the immune response (antigen presentation and immune cell activation), and its long half-time of 15.4 days, ipilimumab can used as an induction therapy, following by the PD1 monoclonal antibody. This phase I study is aimed to evaluated the safety and efficacy of CTLA-4 antibody followed by PD-1 antibody in patients with recurrent or metastatic non-small cell lung cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors.
   Melaiu O, Lucarini V, Cifaldi L, Fruci D. · · 2019 · cited 324× · PMID 32038612 · DOI 10.3389/fimmu.2019.03038
2. Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma.
   Wang X, Guo G, Guan H, Yu Y, et al · · 2019 · cited 204× · PMID 30777100 · DOI 10.1186/s13046-019-1085-3
3. Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy.
   Boyero L, Sánchez-Gastaldo A, Alonso M, Noguera-Uclés JF, et al · · 2020 · cited 78× · PMID 33322522 · DOI 10.3390/cancers12123729
4. Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?
   Chocarro de Erauso L, Zuazo M, Arasanz H, Bocanegra A, et al · · 2020 · cited 58× · PMID 32317979 · DOI 10.3389/fphar.2020.00441
5. Combination checkpoint inhibitors for treatment of non-small-cell lung cancer: an update on dual anti-CTLA-4 and anti-PD-1/PD-L1 therapies.
   Puri S, Shafique M. · · 2020 · cited 29× · PMID 32158484 · DOI 10.7573/dic.2019-9-2
6. The role and therapeutic implications of T cells in cancer of the lung.
   Neeve SC, Robinson BW, Fear VS. · · 2019 · cited 27× · PMID 31485330 · DOI 10.1002/cti2.1076
7. The Comprehensive "Omics" Approach from Metabolomics to Advanced Omics for Development of Immune Checkpoint Inhibitors: Potential Strategies for Next Generation of Cancer Immunotherapy.
   Yoon SJ, Lee CB, Chae SU, Jo SJ, et al · · 2021 · cited 13× · PMID 34203237 · DOI 10.3390/ijms22136932
8. Harnessing NK Cell Checkpoint-Modulating Immunotherapies.
   Chauhan SKS, Koehl U, Kloess S. · · 2020 · cited 11× · PMID 32640575 · DOI 10.3390/cancers12071807