Table 3.

KRAS, NRAS, BRAF, PIK3CA, and EGFR point mutations and MET amplification status in tumor biopsies before and during treatment with Sym004 in patients with metastatic colorectal cancer

KRAS, NRAS, BRAF, PIK3CA, EGFR point mutationsaMET gene copy-number alterationsa
PatientDose (mg/kg)BaselinePrior to 5th infusionBaselinePrior to 5th infusionResponsePFS (mo)
112Wild-typeWild-typeDiploidPR6.7
29Wild-typeWild-typePolysomy (G:CN 0.9)DiploidPR5.3
312Wild-typePolysomy (G:CN 0.7)PRc5.0
512EGFR c.1474A>CDiploidPR5.0
712Loss of METbSD3.2
1012NRAS c.35G>TPolysomy (G:CN 0.8)SD3.3
1112PIK3CA c.1624G>APIK3CA c.1624G>ADiploidSD3.2
1412Wild-typePolysomy (G:CN 0.8)SD3.1
169DiploidPDd0.9
1712KRAS c.183A>CPolysomy (G:CN 0.9)SD7.1
1812PIK3CA c.1633G>ASD2.6
1912Wild-typeKRAS c.35G>C; c.183A>CPolysomy (G:CN 0.8)DiploidPDd1.2
2212KRAS c.35G>ADiploidSD4.8
2412Wild-typeWild-typeDiploidDiploidSD3.2
2512KRAS c.35G>ALoss of METbAmplified (G:CN 15.0)SD2.6
2612Wild-typeWild-typeDiploidDiploidSD1.3
289Wild-typeWild-typeDiploidLoss of METbSD3.0
2912Wild-typePolysomy (G:CN 0.9)PD1.3
309Wild-typeDiploidSD2.6
3212Wild-typeDiploidPD1.4
359BRAF c.1799T>APD1.5
3612Wild-typeDiploidPD0.7
3712Wild-typeNRAS c.183A>TDiploidPolysomy (G:CN 0.9)PD1.2
3812Wild-typeWild-typeDiploidPolysomy (G:CN 1.7)PD1.4
419Wild-typeDiploidPDc,d1.0
4212Wild-typeDiploidPDc,d0.8

Abbreviations: G:CN, MET gene to chromosome 7 copy-number ratio; wild-type, no point mutations detected in analyzed KRAS, NRAS, BRAF, PIK3CA, and EGFR exons; —, biopsy not evaluable; PD, progressive disease; PR, partial response; SD, stable disease.

  • aAnalyses based on a minimum of 20% neoplastic cells in a corresponding hematoxylin and eosin–stained slide.

  • bDiploid with a focal heterozygous gene loss.

  • cUnconfirmed PR or PD, as per RECIST criteria.

  • dClinical assessment of PD.