Extended Data Table 3. Primary outcome measures for each drug-biomarker cohort in NLMT.
Number of patients in the intention-to-treat (ITT) and per protocol populations are shown. For OR and DCB, the observed number is reported together with the denominator that shows the number of patients currently with sufficient follow-up data to be included in the analysis. Bayesian estimates of the true OR rate and DCB rate, given the current data and minimally informative priors, are reported together with 95% credible intervals (CrI). For PFS, Bayesian estimates of the true median PFS in months, given the current data and minimally informative priors, are reported together with 95% credible interval. For closed cohorts, the Bayesian PP is reported for primary outcomes, showing the probability that the true value is greater than the pre-specified clinically relevant targets as follows: OR and/or DCB rates of 30% for B2S, A1, D2, G1, B1, F1-F4; median PFS of 3 months for C2 and C6. For open cohorts, the PPoS is reported for primary outcomes, showing the probability of a go decision when the cohort reaches n = 30, given the current observed data, with pre-specified clinical relevant targets as follows: OR and/or DCB rates of 30% for B2D, D1, D3, and 40% for E2; median PFS of 3 months for C1, C3-C5.
| Cohort | ITT | Per Protocol | Median PFS (months) l95%Crlf | PPoS | PP | Observed DCB | DCB rate estimate (95%Crl) | PPoS | PP | Observed OR | OR rate eslimate (95%Crl) | PPoS | PP |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cell cycle progression Rb proficient | |||||||||||||
| Palbociclib-LUSC CDKN2A loss (C1) | 27 | 25 | 42 (2.7 - 7.2) |
>0.99 | (-) | 4/18 | 24% (9 - 48) |
(-) | (-) | 0/19 | 3% (0-17) |
(-) | (-) |
| Palbociclib-LUAD CDKN2A loss (C2) | 32 | 30 | 3.3 (2.3 - 5.0) |
(-) | 069 | 8/29 | 29% (15 - 46) |
(-) | (-) | 1/27 | 6% (1-18) |
(-) | (-) |
| Palboclclib-CDK4 amplification (C3) | 12 | 11 | 22 (1.1-5.2) |
0.18 | (-) | 0/8 | 7% (0-34) |
(-) | (-) | 0/8 | 7% (0 - 34) |
(-) | (-) |
| Palbociclib-CCND1 amplification (C4) | 22 | 18 | 3.7 (2.3 - 6,5) |
0.85 | (-) | 2/15 | 16% (4 - 38) |
(-) | (-) | 0/15 | 4% (0-21) |
(-) | (-) |
| RAS activation | |||||||||||||
| Palbociclib-KRAS mutation+ dual STK11 loss (C5) | 15 | 12 | 26 (1.5 - 5.0) |
0.27 | 1/11 | 14% (2 - 39) |
(-) | (-) | 0/12 | 5% (0 - 25) |
(-) | (-) | |
| Palbociclib-KRAS mutation (C6) | 33 | 30 | 5.3 (3.8 - 7.9) |
(-) | >0.99 | 12/30 | 40% (25- 53) |
(-) | (-) | 1/30 | 5% (1-17) |
(-) | (-) |
| Vistusertib-KRAS mutation + dual STK11 loss (B2D) | 28 | 25 | 2.9 (2.0 - 4.6) |
(-) | 6/25 | 25% (12 - 44) |
0.13 | (-) | 2/25 | 10% (2 - 25) |
O.01 | (-) | |
| Vistusertib-STKl l loss (B2S) | 19 | 17 | 23 (1.5 - 3.8) |
(-) | 2/17 | 15% (4 - 35) |
(-) | 006 | 0/17 | 4% (0 - 19) |
(-) | O.01 | |
| Selumetinib-LUAD NF1 loss(E2) | 14 | 14 | 5.3 (3.2 - 10.0) |
(-) | 7/14 | 50% (27 - 73) |
ose | (-) | 4/14 | 31% (12 - 55) |
0.17 | (-) | |
| RTK Signalling | |||||||||||||
| AZD4547-FGFR mutations/translocations (A1) | 5 | 5 | 5.6 (2.4 - 19.0) |
(-) | (-) | 1/5 | 26% (4 - 64) |
(-) | 0.42 | 1/5 | 26% (4 - 64) |
(-) | 0.42 |
| Crizotlnib-Met amplification (D1) | 19 | 16 | 3.8 (2.3 - 7.2) |
(-) | (-) | 2/14 | 17% (4-41) |
007 | (-) | 0/13 | 5% (0 - 23) |
<0.01 | (-) |
| Crizotlnib-ROS fusion (D2) | 8 | 8 | 44.6 (16 5- 192.7) |
(-) | (-) | 6/8 | 71% (40 - 93) |
(-) | >0.99 | 5/7 | 68% (35 - 92) |
(-) | 0.99 |
| Crizotlnib-Met eKon 14 skipping mutations (D3) | 13 | 13 | 12.5 (6 4 - 29.7) |
(-) | (-) | 7/10 | 68% (39 - 89) |
>0 99 | (-) | 8/12 | 65% (39 - 86) |
>0.99 | (-) |
| Osimertinib-EGFR T790M (G1) | 10 | 10 | 15.5 (8.5 - 32.6) |
(-) | (-) | 9/10 | 85% (59 - 98) |
(-) | >0.99 | 8/10 | 76% (48 - 94) |
(-) | =0.99 |
| PI3K / PTEN / AKT i mTOR | |||||||||||||
| Vlstuser1lb-TSC1/2 mutation (B1) | 5 | S | 2.1 (1.0 - 6.2) |
(-) | (-) | 0/5 | 11% (0 - 46) |
(-) | 0.12 | 0/5 | 11% (0-46) |
(-) | 0.12 |
| Capivasertlb-LUSC PIK3CA mutation (F1) | 5 | 4 | 1.9 (0.8 - 6.3) |
(-) | (-) | 0/4 | 13% (1 - 52) |
(-) | 0-17 | 0/4 | 13% (1 -52) |
(-) | 0.17 |
| Capivasertlb-LUSC PI3K amplification (F2) | 14 | 12 | 2.1 (1.2 - 4.1) |
(-) | (-) | 1/11 | 14% (2 - 39) |
(-> | 0-09 | 0/12 | 5% (0 - 25) |
(-) | O.01 |
| Caplvasertib-LUAD with aberrations PI3K/PTEN/AKT (F3) | 12 | 11 | 20 (1.0 - 4.8) |
(-) | (-) | 0/8 | 7% (0-34) |
(-) | 004 | 0/8 | 7% (0 - 34) |
(-) | 0.04 |
| Capivasertlb-LUSC PTEN loss (F4) | 4 | 4 | 4.6 (1.4 - 31.6) |
(-) | (-) | 0/2 | 21% (1-71) |
(-) | 0.34 | 0/4 | 13% (1 -52) |
(-) | 0.17 |