Table 2.

Initial substudies in Lung-MAP

Initial estimated patients (phase II/III)
Drug (TT, NMT) manufacturerSubstudy regimensMechanism of actionTarget/biomarkersInitial estimated prevalenceEstimated duration in months (phase II/III)Scientific rationale
Taselisib (GDC-0032)
TT vs. CTP13K Inhibitor
 (β-isoform Sparing)
  • More potent against PIK3CA mutant than wild-type in vitro (30)

  • Promising preliminary clinical activity in PIK3CA mutant cancers, including SCC (30, 31); early data suggest that taselisib is less toxic than other PI3K inhibitors

Palbociclib PfizerTT vs. CTCDK4/6
 (highly selective)

  • Activity in RB+ cell lines and xenografts (32–34)

  • Showed clinical activity (SD prolongation) as monotherapy (32–34)

  • Very active in combination with letrozole in ER+, HER2 breast cancer (32–34)

AZD4547 AstraZenecaTT vs. CTFGFR kinase

  • In vitro activity in FGFR amplified, mutated, gene translocated cell lines (35, 36)

  • Amplification of FGFR1 in Chinese NSCLC patient tumors, particularly in SCC patients (36)

  • Potent tumor stasis or regression in xenograft models of SCC NSCLC (35, 36)

Rilotumumab [AMG102] Amgen [In process of being replaced, Amgen has decided not to continue development for cancer indications]TT + E vs. EAnti-HGFc-MET

  • EGFR and MET may cooperate in driving tumorigenesis; well-tolerated in phase I study in patients with advanced solid tumors; evidence of prolongation of stable disease in these patients (37)

  • Positive results in phase II trial in gastric cancer; has been in registration trial in gastric cancer (with CT; ref. 38)

NMT vs. CTAnti–PD-L1Nonmatch

Activity in a
  • Anti-PD-1 and anti–PD-L1 monoclonal antibodies are active in NSCLC, work is ongoing to define selected populations that will derive most benefit from treatment with these agents (39, 40)

NOTE: Column 1 lists the four targeted therapies (TTs) and one nonmatch therapy (NMT) that comprise the initial set of drugs being evaluated in Lung-MAP. Column 2 shows the arms of the substudies. Three of the TTs are being evaluated as monotherapy against chemotherapy (docetaxel; CT); the fourth is being evaluated in combination with erlotinib (E) against E. Column 3 lists the putative mechanisms of action of the drugs, which form the basis for using these drugs against the targets with corresponding biomarkers listed in Column 4. Column 5 shows the prevalence of the target/biomarkers in lung SCC as estimated using FMI's FoundationOne NGS platform in 108 lung SCC samples for PIK3CA, CDK4/6, and FGFR (see Fig. 3). c-MET overexpression prevalence is estimated from previous studies of c-MET inhibitors. The estimated prevalence for the nonmatch substudy is 100% less the prevalence for the other targets. Column 6 shows the initial expected size and duration of the phase II and III studies for each drug. Column 7 is a brief description of the evidence supporting testing the drugs in Lung-MAP. Additional information on the biologic activity, clinical efficacy, and toxicity of these drugs can be found in the references cited in this table.

Abbreviations: CCND, cyclin D gene; CDK4/6, cyclin-dependent kinases 4 and 6; ER, estrogen receptor; HGF, hepatocyte growth factor; PD-1, programmed death receptor 1; PD-L1, programmed death receptor ligand 1; PIK3CA, gene for PI3K catalytic subunit α; RB, retinoblastoma gene; SD, stable disease.