Table 4 Selected ongoing clinical trials investigating immunotherapy in combination with agents targeting resistance mechanisms

From: Immune checkpoint inhibitors for the treatment of MSI-H/MMR-D colorectal cancer and a perspective on resistance mechanisms

Clinicaltrial.gov identifier

Trial design

Rationale/phase of trial/current status

Study group

NCT03095781

Pembrolizumab and XL888 (HSP90 inhibitor) in patients with advance gastrointestinal cancers

Enhancing immune response by upregulating interferon response/Phase 1b/recruiting

Previously treated advanced gastrointestinal cancers

NCT02675946

CGX1321 in subjects with advanced solid tumours and CGX1321 with pembrolizumab in subjects with advanced gastrointestinal tumours (Keynote 596)

Combination of checkpoint inhibitor with Wnt inhibitor to enhance the efficacy/Phase 1b/recruiting

Previously treated advanced gastrointestinal cancers

NCT02947165

Phase I/Ib study of NIS793 in combination with PDR001 in patients with advanced malignancies

Combination of TGF-β inhibitor with anti-PD-1 inhibitor/Phase 1b/recruiting

Advanced solid tumours

NCT03638297

PD-1 antibody combined with COX inhibitor in MSI-H/MMR-D or high tumour mutation burden colorectal cancer

Combining COX-2 inhibitor with an anti-PD1 inhibitor to enhance the efficacy/Phase 2/recruiting

Previously treated MSI-H colorectal cancer

NCT03607890

A study of nivolumab and relatlimab in advanced MMR-D cancers resistant to prior PD-(L)1 inhibitor

Combining anti-LAG3 antibody with an anti-PD1 inhibitor to enhance the efficacy/Phase 2/recruiting

MSI-H colorectal cancer with previous PD-(L)1 exposure

NCT03608046

A study of subcutaneous nivolumab monotherapy with or without recombinant human hyaluronidase PH20 (rHuPH20)

Combining stroma modifying agent with anti-PD1 to enhance the efficacy/Phase 1/recruiting

Previously treated advanced gastrointestinal cancers

NCT03126110

Phase 1/2 study exploring the safety, tolerability, and efficacy of INCAGN01876 combined with immune therapies in advanced or metastatic malignancies

Combining anti-human glucocorticoid-induced tumour necrosis factor receptor with combination of a checkpoint inhibitor to obtain more sustained response

Advanced solid tumours

  1. HSP Heat-shock protein, COX Cyclooxygenase, LAG3 Lymphocyte-activation gene 3, PD-1 Programmed cell death protein 1, MSI-H Microsatellite instability high, MMR-D Mismatch repair-deficient