Table 3 Clinical trials evaluating the combination of KRAS inhibitors with immune checkpoint inhibitors.

From: Oncogenic KRAS mutations drive immune suppression through immune-related regulatory network and metabolic reprogramming

Drug

Combination

Cancer Type

Study overview

Clinical trial

Sotorasib

Pembrolizumab (PD-1)

mCRC、NSCLC

Phase 1: safety and tolerability

CodeBreak101 (NCT04185883)

Atezolizumab (PD-L1)

Phase 2: ORR、DCR、DoR

Adagrasib

Pembrolizumab (PD-1)

NSCLC

Phase 1: safety and tolerability

KRYSTAL-1 (NCT03785249)

Phase 2: ORR、DCR、DoR

LY3537982

Pembrolizumab (PD-1)

NSCLC

Phase 1: safety and tolerability

LOXO-RAS-20001(NCT04956640)

Phase 2: ORR、DCR DoR

JDQ443

Tislelizumab (PD-1)-/+

Solid tumor

Phase 1/2: safety, tolerability, and tumor activity

KontRASt-01 (NCT04699188)

TNO155(SHP2i)

Adagrasib

Pembrolizumab (PD-1)

NSCLC

Phase 2: safety and tolerability of monotherapy and combination in advanced NSCLC and any PD-L1 TPS candidates for first-line treatment

Phase 3: compare efficacy of adagrasib plus pembrolizumab vs. pembrolizumabin first-line setting with tumors PD-L1 TPS ≥ 50%

KRYSTAL-7 (NCT04613596)

GDC-6036

Atezolizumab (PD-L1)

 

Phase 1: safety and tolerability

NCT04449874

Phase 2: ORR、PFS

MK-1084

Pembrolizumab (PD-1)

NSCLC

Phase 1: safety and tolerability

NCT05067283

MK-1084

Pembrolizumab (PD-1)

NSCLC (n = 600) PD-L1 TPS ≥ 50%

Phase 1: safety and tolerability

NCT06345729

RMC-6291(G12C)or RMC-6236(multi) Revolution Medicines

Pembrolizumab (PD-1) −/+chemotherapy

NSCLC

Phase 1/2: safety, tolerability, and tumor activity combined with standard of care (PD-1-/+chemo)

NCT06162221

IBI351

Sintilimab (PD-1)−/+ chemotherapy

NSCLC

Phase 1: safety and tolerability of monotherapy and combination in NSCLC Phase 2/3: efficacy

NCT05504278

  1. ORR objective response rate, DCR disease control rate, DOR duration of response, PFS progression-free survival, TPS tumor proportion score.
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