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TRILACICLIB DECREASES MYELOSUPPRESSION IN EXTENSIVE-STAGE SMALL CELL LUNG CANCER (ES-SCLC) PATIENTS RECEIVING FIRST-LINE CHEMOTHERAPY PLUS ATEZOLIZUMAB DAVEY DANIEL1; VLADIMER KUCHAVA2; IGOR BONDARENKO3; OLEKSANDR IVASHCHUK4; DAVID SPIGEL5; ANIRUDHA DASGUPTA6; SREEKANTH REDDY7; TAMAR MELKDZE8; JANA JAAL9; IVETA KUDABA10; LOWELL HART11; AMIRAN MATITASHVILI12; KRASSIMIR KOYNOV13; JESSICA A. SORRENTINO14; ANNE Y. LAI14; ZHAO YANG14; STEVEN WOLFE14; RAJESH MALIK14; SHANNON R. MORRIS14; JOYCE M. ANTAL14; AND JEROME GOLDSCHMIDT15 1 SARAH CANNON RESEARCH INSTITUTE, TENNESSEE ONCOLOGY-CHATTANOOGA, CHATTANOOGA, TN, USA; 2 LTD CLINICAL ONCOLOGY CENTER, TBILISI, GEORGIA; 3 DNIPROPETROVSK CITY MULTISPECIALTY CLINICAL HOSPITAL, DNIPRO, UKRAINE; 4 CHERNIVTSI REGIONAL CLINICAL ONCOLOGY CENTER, CHERNIVTSI, UKRAINE; 5 SARAH CANNON RESEARCH INSTITUTE, NASHVILLE, TN, USA; 6 MILLENNIUM ONCOLOGY, HOUSTON, TX, USA; 7 NORTHSIDE HOSPITAL, INC, ATLANTA, GA, USA; 8 LTD RESEARCH INSTITUTE OF CLINICAL MEDICINE, TBILISI, GEORGIA; 9 TARTU UNIVERSITY HOSPITAL, HEMATOLOGY - ONCOLOGY CLINIC, TARTU, ESTONIA; 10 RIGA EAST UNIVERSITY HOSPITAL, LLC, LATVIAN ONCOLOGY CENTER, RIGA, LATVIA; 11 FLORIDA CANCER SPECIALISTS, FORT MYERS, FL, USA; 12 LTD CANCER RESEARCH CENTRE, TBILISI, GEORGIA; 13 MULTIPROFILE HOSPITAL FOR ACTIVE TREATMENT ‒ SERDIKA, SOFIA, BULGARIA; 14 G1 THERAPEUTICS, RESEARCH TRIANGLE PARK, NC, USA; 15 BLUE RIDGE CANCER CARE, BLACKSBURG, VA, USA

TABLE 1 STUDY OBJECTIVES AND ENDPOINTS DOSE EXPOSURE AND DOSE MODIFICATIONS TABLE 4 SUMMARY OF TEAES OCCURRING IN ≥ 15% OF PATIENTS IN EITHER ARM (SAFETY ANALYSIS SET) FLOW CYTOMETRY BACKGROUND Primary Objective Primary Endpointsa • Patients receiving trilaciclib received a higher relative dose intensity of chemotherapy compared with those E/P/A + Placebo E/P/A + Trilaciclib 240 mg/m2 • The addition of trilaciclib to etoposide, carboplatin, and atezolizumab treatment increased the number of receiving placebo (n = 53) (n = 52) circulating activated CD8+ T and Th1 cells during chemotherapy, and increased the ratio of total and activated Evaluate the potential of trilaciclib to reduce chemotherapy- • Duration of severe (Grade 4) neutropenia in cycle 1 CD8+ T cells to regulatory T cells in both the induction and maintenance phases of treatment in peripheral blood • Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPCs) causes multilineage induced myelosuppression • Occurrence of severe (Grade 4) neutropenia • The diff erence in relative dose intensity was due to fewer patients having etoposide or carboplatin dose All Grades Grade ≥ 3 All Grades Grade ≥ 3 myelosuppression, which may antagonize the intended eff ects of chemotherapy/immune checkpoint reductions and/or cycle delays with trilaciclib compared with placebo (Table 3) (Figure 6A‒D) a Any TEAE 52 (98.1) 46 (86.8) 49 (94.2) 33 (63.5) inhibitor combinations1,2 Key Secondary Objectives Key Secondary Endpoints • • The frequency of dose reductions for etoposide or carboplatin over time (event rate) was also lower for patients Patients treated with trilaciclib had signifi cantly higher numbers of expanded T-cell clones than patients treated • Occurrence of RBC transfusions on/after week 5 Hematologica • Current supportive therapies (eg, growth factors and transfusions) are lineage specifi c and are administered after who received trilaciclib compared with placebo with placebo (P = 0.01; Figure 6E) Evaluate the potential of trilaciclib to reduce chemotherapy- • Occurrence of G-CSF use Anemia 33 (62.3) 16 (30.2) 19 (36.5) 9 (17.3) chemotherapy damage has occurred3 • induced myelosuppression and its consequences • All-cause dose reductions (event rate) Neutropenia 40 (75.5) 32 (60.4) 22 (42.3) 11 (21.2) Regardless of treatment, patients with high levels of T-cell clones had longer PFS (Figure 6F) TABLE 3 SUMMARY OF DOSE EXPOSURE AND DOSE MODIFICATIONS (SAFETY ANALYSIS SET) Thrombocytopenia 35 (66.0) 21 (39.6) 12 (23.1) 1 (1.9) • Trilaciclib is a highly potent, selective, reversible, transient cell cycle inhibitor that preserves HSPCs during • OSb Leukopenia 20 (37.7) 11 (20.8) 10 (19.2) 3 (5.8) chemotherapy (myelopreservation) and enhances antitumor immunity 3,4 (Figure 1) E/P/A + Trilaciclib FIGURE 6 T-CELL SUBPOPULATIONS AND CLONAL EXPANSION Supportive Secondary Objectives Supportive Secondary Endpoints 2 E/P/A + Placebo 240 mg/m Nonhematologica • ELL UBPOPULATIONS As previously reported, a randomized, double-blind, phase 1b/2 trial demonstrated the myelopreservation benefi ts • ORR (INV assessed) (n = 53) (n = 52) Nausea 18 (34.0) 1 (1.9) 20 (38.5) 0 T-C S Evaluate the antitumor activity of trilaciclib in combination of trilaciclib when combined with standard cytotoxic chemotherapy for patients with newly diagnosed extensive- • Duration of OR (INV assessed) Fatigue 20 (37.7) 2 (3.8) 16 (30.8) 1 (1.9) A Activated CD8+ T cells B Activated Th1 cells Trilaciclib 5 with E/P/A Duration of exposure (induction + maintenance) 3 2 stage small cell lung cancer (ES-SCLC) • PFS (INV assessed) Dyspnea 12 (22.6) 3 (5.7) 8 (15.4) 3 (5.8) Median (range) days 182 (21‒705) 205 (42‒660) Placebo Median (range) cycles 8 (1‒28) 8 (2‒31) Dizziness 8 (15.1) 1 (1.9) 9 (17.3) 0 • Preclinical studies have shown that the immune-modulating eff ects of trilaciclib may enhance the effi cacy of • Occurrence and severity of AEs 2 Determine the safety and tolerability of trilaciclib in combination Constipation 12 (22.6) 1 (1.9) 5 (9.6) 0 chemotherapy/immune checkpoint inhibitor combinations6 • Relative dose intensity Median relative dose intensity, % 1 with E/P/A Dehydration 11 (20.8) 3 (5.7) 5 (9.6) 0 1 Etoposide 92.3 98.1 • Dose modifi cations Asthenia 8 (15.1) 2 (3.8) 8 (15.4) 4 (7.7) • This global, randomized, double-blind, placebo-controlled, multicenter, phase 2 study (NCT03041311) assessed Carboplatin 93.3 98.8 A Activated CD8+ T cells B Activated Th1 cells Trilaciclib old change from baseline) Diarrhea 6 (11.3) 0 9 (17.3) 1 (1.9) 3old change from baseline) 2 the potential of trilaciclib to reduce the incidence and consequences of chemotherapy-induced myelosuppression • Occurrence of G-CSF use, ESA use, platelet transfusions, and Atezolizumab (induction + maintenance) 95.0 96.3 0 0 g (f

Cough 8 (15.1) 0 7 (13.5) 1 (1.9) og (f Placebo L Assess eff ect of trilaciclib on multiple lineages and current RBC transfusions Lo in patients with newly diagnosed ES-SCLC treated with etoposide, carboplatin, and atezolizumab (a programmed a 4 (7.7) 2–1 –1 standard of care interventions to treat myelosuppression • ANC, hemoglobin, platelet counts, and lymphocyte counts Dose reductions, n (%) Pneumonia 8 (15.1) 8 (15.1) 7 (13.5) death-ligand 1 inhibitor) iC1D1 mC1D1mC5D1PTV + 90 iC1D1 mC1D1 mC5D1 PTV + 90 over time Etoposide 14 (26.4) 3 (5.8) Pyrexia 5 (9.4) 0 8 (15.4) 0 1 Carboplatin 13 (24.5) 1 (1.9) 1 CD8+ T cells/regulatory T cells Activated CD8+ T cells/regulatory T cells Samples Decreased appetite 9 (17.0) 0 4 (7.7) 0 C D Analyzed, n Trilaciclib Placebo IGURE RILACICLIB IRST IN LASS RANSIENT ELL YCLE NHIBITOR Exploratory Objectives Exploratory Endpoints 2 4 F 1 T : A F - -C T C C I a TEAEs are presented by Preferred Term. iC1D1 38 29 Cycle delays, n (%) 31 (58.5) 18 (34.6) old change from baseline) old change from baseline) 0 30 E/P/A, etoposide, carboplatin, and atezolizumab; TEAE, treatment-emergent adverse event. mC1D1 25 22 g (f

Evaluate the eff ects of trilaciclib on PROs • Assess change from baseline in FACT instrument scores b og (f L M All-cause dose reductions Lo 1 2 mC5D1 16 12 G2 Trilaciclib Event rate (per 100 cycles) 8.5 2.1 EALTH ELATED UALITY OF IFE –1 –1 Normal (CDK4/6 inhibitor) • Change from baseline of immune cell subsets H -R Q L iC1D1 mC1D1mC5D1PTV + 90 1 iC1D1 mC1D1 mC5D1 PTV + 90 PTV + 90 7 9 cell Explore changes in peripheral blood immune subsets by a No dose reductions were allowed for atezolizumab or trilaciclib during the study. 0 • Relationship between immune cell subsets and biological/ b

old change from baseline) CD8+ T cells/regulatory T cells old change from baseline) Activated CD8+ T cells/regulatory T cells S G1 immunophenotyping Based on intention-to-treat analysis data set (E/P/A + placebo, n = 53; E/P/A + trilaciclib, n = 54); data reported for induction period only, unless otherwise stated. • Enrolled patients had a moderate level of functioning and were moderately symptomatic at baseline as measured C D 0 clinical endpoints E/P/A, etoposide, carboplatin, and atezolizumab. 2 4 og (f og (f

by the validated FACT-L and FACT-An instruments L L –1 a To adjust for the multiple comparisons from the primary and key secondary endpoints, a Hochberg-based gatekeeping procedure was utilized to control the overall type I error rate at a –1 3 1-sided 0.025 level. • Trilaciclib improved the patient experience by delaying deterioration of patient functioning and symptom iC1D1 mC1D1mC5D1PTV + 90 iC1D1 mC1D1 mC5D1 PTV + 90 YELOPRESERVATION 1 b Though OS was listed as a key secondary endpoint it was not built into the multiplicity control; the intention of the OS analysis was to show 'no harm'. M 2 Transient G1 arrest during chemotherapy AE, adverse event; ANC, absolute neutrophil count; E/P/A, etoposide, carboplatin, and atezolizumab; ESA, erythropoiesis-stimulating agent; FACT, Functional Assessment of Cancer Therapy; measures over time, compared with placebo. Overall, the benefi t of trilaciclib was seen with functional well-being, Normalized mean cell counts for (A) activated CD8+ T cells (CD38+HLADR+CD3+CD8+) and (B) activated Th1 cells (CXCR3+CXCR6-CD38+HLADR+CD3+CD4+). Normalized mean ratios of G-CSF, granulocyte colony-stimulating factor; INV, investigator; OR, objective response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PRO, patient-reported • Trilaciclib reduced both the duration of severe neutropenia in cycle 1 (P < 0.0001), a surrogate for febrile 1 Preserves immune system function and Proactive protection of HSPC prevents quality of life measures specifi c for patients with lung cancer, and symptoms and impact of fatigue, as well as absolute (C) CD8+/regulatory T cells and (D) activated CD8+/regulatory T cells. Regulatory T-cell population is defi ned as CD45+CD25+CD127lowCD3+CD4+. Cell populations in whole blood outcome; RBC, red blood cell. neutropenia and infections, and the occurrence of severe neutropenia (P < 0.0001), compared with placebo were0 analyzed by fl ow cytometry at the indicated time points (C, cycle; D, day; i, induction; m, maintenance; PVT, post-treatment visit + 90 days). Error bars represent 95% CI. directly enhances immune response chemotherapy-induced myelosuppression with symptoms and eff ects on physical and functional well-being due to anemia (Figure 4) old change from baseline) old change from baseline) 0 • (Figure 3) A. Alters the proliferation kinetics and Neutrophil A. Reduces occurrence and duration of Data presented are from the following data cuts: Aug 17, 2018 for fi nal myelosuppression endpoints (ie, after all og (f og (f • Statistically signifi cant diff erences between the trilaciclib and placebo treatment groups were observed for L L –1 composition of intratumor T-cell subsets severe neutropenia ELL LONAL XPANSION T cell patients had the opportunity to receive 4 cycles of induction therapy) and Aug 05, 2019 for all other endpoints T-C–1 C E to favor increased effector function Erythrocyte • Although not statistically signifi cant, trilaciclib also reduced the need for red blood cell (RBC) and platelet Functional Well-being, Lung-Trial Outcome Index, and FACT-An total score (Figure 4) iC1D1 mC1D1mP =C5D 0.011PTV + 90 iC1D1 mC1D1 mC5D1 PTV + 90 B. Reduces anemia and thrombocytopenia EF B. Enhances T-cell activation transfusions and the use of granulocyte colony-stimulating factor and erythropoiesis-stimulating agents, 250 100 High = above median (n = 28) Platelets SSESSMENTS C. Reduces need for supportive care (growth A Low = below median (n = 27) HSPC compared with placebo (Figure 3) IGURE IME TO ONFIRMED ETERIORATION OF ATIENT UNCTIONING AND YMPTOM EASURES C. Increases antigen processing and factors, transfusions, chemotherapy dose F 4 T C D P F S M presentation on tumor cells T lymphocyte reductions) • Complete blood counts were obtained on days 1, 3, 8, and 15 of each cycle of trilaciclib/placebo plus etoposide, HR (95% CI) = 0.63 (0.35–1.12) % Tumor Domain No. of Events Median TTD, Months HR HR (95% CI) 200 75 Binary log-rank test: P = 0.12 D. Reduces immunosuppressive function of B lymphocyte D. Preserves lymphocytes carboplatin, and atezolizumab (induction) or atezolizumab (maintenance) FIGURE 3 SUMMARY OF MYELOSUPPRESSION ENDPOINTS (ITT ANALYSIS SET)

regulatory cells Trilaciclib/Placebo Trilaciclib/Placebo vival, • Adverse events (AEs) were graded according to the National Cancer Institute’s Common Terminology Criteria for FACT-Ga 13/22 NYR/NYR 0.58 (0.29-1.15) CDK, cyclin-dependent kinase; HSPC, hematopoietic stem and progenitor cell. 0 Primary endpoints 50 AEs version 4.03 Mean duration (days) of Grade 4 SN in cycle 1 PWB 17/22 NYR/NYR 0.82 (0.44-1.56) 150 4.0 P < 0.0001 • Patient-reported outcomes were assessed using Functional Assessment of Cancer Therapy-Lung (FACT-L) and FWB 15/30 8.57/3.53 0.40 (0.22-0.75) EWB 15/15 NYR/NYR 1.09 (0.53-2.25) Functional Assessment of Cancer Therapy-Anemia (FACT-An) instruments, administered to patients on day 1 of 1.9 ogression-free sur 25

100 Pr % of patients with Grade 4 SN SWB 19/18 NYR/NYR 1.02 (0.53-1.95) METHODS each cycle and at posttreatment visits 49.1 P < 0.0001 . of expanded clones FACT-L 17/23 NYR/7.16 0.70 (0.38-1.32) No • Tumor response was assessed per Response Evaluation Criteria in Solid Tumors version 1.1 1.9 LCS 13/13 NYR/NYR 1.08 (0.50-2.33) 0 % of patients with FN 50 0246810 PATIENTS 5.7 Lung-TOI 11/24 NYR/7.95 0.42 (0.21-0.87) Neutrophil lineage Months • Key eligibility criteria: FACT-An 16/28 NYR/4.17 0.52 (0.28-0.96) 29.6 No. at risk RESULTS % of patients with G-CSF administration Fatigue 20/28 7.20/2.60 0.66 (0.37-1.18) 0 High 28 27 18 8 5  Aged ≥ 18 years 47.2 Placebo Trilaciclib Low 26 22 7 6 4  Chemotherapy and checkpoint inhibitor naïve Anemia-TOI 19/27 7.20/3.84 0.65 (0.36-1.18) ATIENT ISPOSITION AND ASELINE HARACTERISTICS (n = 26) (n = 29)  P D B C 18.5 0.4 0.6 0.8 1 1.67 2.5 Histologically or cytologically confi rmed ES-SCLC with measurable disease % of patients with Grade 3/4 anemia (E) The number of expanded T-cell clones was determined by the diff erential abundance analysis of T-cell receptor βsequences in whole blood from patients at cycle 1, day 1 (C1D1) of  ‒ • As of Aug 05, 2019, 125 patients were screened and 107 eligible patients (intention-to-treat analysis set) 28.3 Trilaciclib better Placebo better maintenance versus C1D1 of induction. Horizontal bars indicate median number of expanded clones in each group. (F) Patients were stratifi ed into low (below median) and high (above Eastern Cooperative Oncology Group Performance Status 0 2 median) number of expanded T-cell clones (median 48 clones for all patients) for Kaplan-Meier analysis of progression-free survival. were randomized to receive trilaciclib (n = 53) or placebo (n = 54) in combination with etoposide, carboplatin, a  Adequate organ function 13.0 FACT-G constitutes the core of FACT-L and FACT-An (not repeated at each assessment). HR, hazard ratio. and atezolizumab % of patients with RBC transfusion ≥ week 5 EWB, Emotional Well-being; FACT-An, Functional Assessment of Cancer Therapy-Anemia; FACT-G, Functional Assessment of Cancer Therapy-General; FACT-L, Functional Assessment of Cancer  Hemoglobin ≥ 9.0 g/dL 20.8 Therapy-Lung; FWB, Functional Well-being; HR, hazard ratio; LCS, Lung Cancer Subscale; NYR, not yet reached; PWB, Physical Well-being; SWB, Social Well-being; TOI, Trial Outcome Index; TTD, time to deterioration.  Absolute neutrophil count ≥ 1.5 × 109 L • 105 patients received ≥ 1 dose of study drug (safety analysis set), and 24 patients are ongoing in the study, RBC lineage 5.6  Platelet count ≥ 100 × 109 L with 11 patients ongoing with atezolizumab treatment in the maintenance phase % of patients with ESA use CONCLUSIONS 11.3 ANTITUMOR EFFICACY  No symptomatic brain metastases • Primary reasons for study discontinuation were similar between treatment arms; across both arms, these were • Investigator-assessed objective response rate (ORR) was comparable between trilaciclib (56.0%) and placebo • Compared with placebo, trilaciclib makes etoposide, carboplatin, and atezolizumab treatment safer and more  No active, known, or suspected autoimmune disease that required systemic treatment in the past 2 years death (n = 65, 60.7%) and withdrawal of patient consent (n = 9, 8.4%) 1.9 % of patients with Grade 3/4 thrombocytopenia (63.5%) treatment groups tolerable by protecting patients from chemotherapy-induced myelosuppression as evidenced by: 37.7 • Baseline demographic and disease characteristics were generally comparable across the treatment groups (Table 2)  Eff ects on neutrophils (statistically signifi cant improvement in primary endpoints of duration of severe STUDY DESIGN • The clinical benefi t rate, including patients with confi rmed complete response, confi rmed partial response, or stable 1.9 neutropenia, and occurrence of severe neutropenia), RBCs (lower rates of Grade 3/4 anemia and transfusions), % of patients with platelet transfusion disease for at least 5 weeks from cycle 1, day 1, was 96.0% with trilaciclib compared with 90.4% with placebo • The study schematic is shown in Figure 2. The study objectives and endpoints are shown in Table 1 TABLE 2 PATIENT DEMOGRAPHIC AND BASELINE DISEASE CHARACTERISTICS (ITT ANALYSIS SET) Platelet lineage 3.8 and platelets (lower rates of Grade 3/4 thrombocytopenia and transfusions) • Median progression-free survival (PFS) was 5.9 (95% CI, 4.2‒7.1) months for trilaciclib compared with •  Fewer supportive care requirements Primary prophylactic hematopoietic growth factors were prohibited in cycle 1; otherwise, standard supportive 0101020 0320 0430 0540 0650 0 60 E/P/A + E/P/A + 5.4 (95% CI, 4.3‒5.7) months for placebo (hazard ratio [HR], 0.83; P = 0.3079; Figure 5)  Fewer chemotherapy dose reductions care was allowed throughout the study Placebo Trilaciclib 240 mg/m2 Total E/P/A + trilaciclib (n = 54) E/P/A + placebo (n = 53) • (n = 53) (n = 54) (N = 107) With a median follow-up of 10.9 months (range, 0.0‒24.3 months), median overall survival (OS) was  Numerically increased relative dose intensities of etoposide, carboplatin, and atezolizumab E/P/A, etoposide, carboplatin, and atezolizumab; ESA, erythropoiesis-stimulating agent; FN, febrile neutropenia; G-CSF, granulocyte colony-stimulating factor; ITT, intention-to-treat; 12.0 (95% CI, 9.6‒16.2) months for trilaciclib compared with 12.8 (95% CI, 7.9‒15.5) months for placebo  Improved overall safety profi le, primarily due to a reduction in high-grade hematologic AEs attributable to FIGURE 2 STUDY SCHEMATIC Median (range) age, years 64 (46‒83) 65 (45‒81) 64 (45‒83) RBC, red blood cell; SN, severe neutropenia. (HR, 0.95; P = 0.9461; Figure 5) cytotoxic chemotherapy Screening Phase Treatment Phase Survival Follow-up Phase Age group, years, n (%) • Validated patient-reported outcome instruments suggest that the addition of trilaciclib improves the patient 18 to < 65 27 (50.9) 27 (50.0) 54 (50.5) SAFETY FIGURE 5 PFS AND OS Induction Part Maintenance ≥ 65 26 (49.1) 27 (50.0) 53 (49.5) experience on chemotherapy • The most common all-grade and Grade ≥ 3 treatment-emergent AEs (TEAEs) occurring during the induction (Cycles 1‒ 4) Part a • ORR, PFS, and OS data demonstrate that trilaciclib does not impair chemotherapy/atezolizumab antitumor effi cacy Male, n (%) 34 (64.2) 41 (75.9) 75 (70.1) and maintenance phases are shown in Table 4 PFS OS HR (95% CI) = 0.83 (0.55‒1.24) HR (95% CI) = 0.95 (0.59‒1.52) 2 1.0 1.0 • Trilaciclib 240 mg/m IV QD Country, n (%) • There were fewer Grade ≥ 3 TEAEs with trilaciclib compared with placebo, mostly due to a lower number of Stratified log-rank test: P = 0.3079 Stratified log-rank test: P = 0.9461 Flow cytometry data suggest that during treatment with etoposide, carboplatin, and atezolizumab, (days 1‒3) + etoposide USA 22 (41.5) 20 (37.0) 42 (39.3) coadministration of trilaciclib can enhance the T-cell immune response 2 Atezolizumab Grade ≥ 3 hematologic AEs 100 mg/m (days 1‒3), c Non-USA 31 (58.5) 34 (63.0) 65 (60.7) 1200 mg Q21D 0.8 0.8 carboplatin AUC5 (day 1), and  Overall Grade ≥ 3 TEAEs: 63.5% with trilaciclib versus 86.8% with placebo Trilaciclib (median = 5.9 months) Trilaciclib (median = 12.0 months) • These data confi rm the myelopreservation benefi ts of trilaciclib observed in another fi rst-line trial of trilaciclib in atezolizumab 1200 mg (day 1)b ECOG PS, n (%) Post- Placebo (median = 5.4 months) Placebo (median = 12.8 months) combination with etoposide and carboplatin in ES-SCLC (NCT02499770)5 as well as in combination with topotecan 0‒1 46 (86.8) 45 (85.2) 92 (86.0)  Drug-related Grade ≥ 3 TEAEs: 51.9% with trilaciclib versus 75.5% with placebo OS Screening a treatment Survival follow-upe PFS 0.6 0.6 7 R 1:1 d 2 7 (13.2) 8 (14.8) 15 (14.0) in patients previously treated for ES-SCLC (NCT02514447) Placebo IV QD visits • 16 patients had TEAEs considered related to trilaciclib (days 1‒3) + etoposide 2 Baseline LDH 100 mg/m (days 1‒3), Atezolizumab  The most common TEAEs considered related to trilaciclib were fatigue (9.6%), nausea (7.7%), and 0.4 0.4 REFERENCES c ≤ carboplatin AUC5 (day 1), 1200 mg Q21D ULN 29 (54.7) 26 (48.1) 55 (51.4) Probability of > ULN 24 (45.3) 25 (46.3) 49 (45.8) anemia and infusion-related reaction (5.8% each); most of these were low grade, with the exception of Probability of 1. Smith RE. J Natl Compr Canc Netw. 2006;4:649-658. 4. Bisi JE, et al. Mol Cancer Ther. 2016;15:783-793. 6. Sorrentino JA, et al. Cancer Res. 2017;77:abstract #5628. and atezolizumab 2. Lyman GH. Oncology (Williston Park). 2006;20:16-25. 5. Weiss JM, et al. Ann Oncol. 2019; In press. 7. Hart LL, et al. J Clin Oncol. 2019;37: 8505. b Grade 3 fatigue (1.9%) 1200 mg (day 1) Missing 0 3 (5.6) 3 (2.8) 0.2 0.2 3. He S, et al. Sci Transl Med. 2017;9:eaal3986. Presence of brain metastases, n (%) 15 (28.3) 15 (27.8) 30 (28.0) • 12 (23.1%) patients in the trilaciclib arm and 11 (20.8%) in the placebo arm had atezolizumab AEs of a Randomization stratifi ed by ECOG PS (0‒1 vs 2) and presence of brain metastases (yes vs no). ACKNOWLEDGEMENTS b During the induction phase of the study, trilaciclib or placebo + E/P/A therapy continues for up to four 21-day cycles or until disease progression per RECIST v1.1, unacceptable toxicity, special interest, which were mostly immune-related 0.0 0.0 • On behalf of the G1T28-05 Study Group, we thank and acknowledge all of the patients, their families, and the global study personnel for participating in the study or discontinuation by the patient or investigator. Smoking history, n (%) c Following the induction phase, patients proceed to the maintenance phase of the study and receive atezolizumab every 21 days until disease progression per RECIST v1.1, unacceptable Never smoked 6 (11.3) 4 (7.4) 10 (9.3) • Serious TEAEs were reported in 32.7% of patients treated with trilaciclib and 47.2% of patients treated with 012345678910 11 12 13 14 15 16 17 18 19 20 21 0 12345678910 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 • Study sponsored by G1 Therapeutics. Medical writing assistance was provided by Alligent Europe (Envision Pharma Group), funded by G1 Therapeutics toxicity, or discontinuation by the patient or investigator. Following disease progression per RECIST v1.1, if the patient appears to be deriving clinical benefi t, if the investigator believes it is Months from randomization date Months from randomization date in the best interest of the patient, and if the patient has provided reconsent, study drug administration can be continued until loss of clinical benefi t. Former or current smoker 47 (88.7) 49 (90.7) 96 (89.7) placebo; 1 (1.9%) serious TEAE (deep vein thrombosis) was considered possibly related to trilaciclib No. of patients at risk: d Trilaciclib 54 51 48 42 36 30 23 21 14 11 9 6 5 4 4 3 3 2 2 0 0 0 54 53 51 49 46 45 42 39 35 32 30 27 23 22 18 17 17 15 9 7 6 5 1 1 1 0 All patients return to the study center for posttreatment visits at 30 (+ 3) and 90 (+ 7) days after the last dose of study drug. Missing 0 1 (1.9) 1 (0.9) Placebo 53 51 49 47 40 31 16 11 10 7 6 6 4 4 4 4 4 2 2 1 1 0 53 51 51 50 46 46 44 38 33 31 29 28 26 23 21 18 16 14 7 3 2 1 1 0 0 0 Corresponding author email address: [email protected] e The survival follow-up phase continues until ≥ 70% of the patients randomized in the study have died. • In the trilaciclib treatment group, there were 2 deaths due to TEAEs: hemoptysis (n = 1) and pneumonia (n = 1), AUC, area under the curve; ECOG PS, Eastern Cooperative Oncology Group Performance Status; E/P/A, etoposide, carboplatin, and atezolizumab; IV, intravenous; Q21D, every 21 days; ECOG PS, Eastern Cooperative Oncology Group Performance Status; E/P/A, etoposide, carboplatin, and atezolizumab; ITT, intention-to-treat; LDH, lactate dehydrogenase; a OS data are not yet mature. QD, once daily; R, randomization; RECIST v1.1, Response Evaluation Criteria in Solid Tumors, Version 1.1. ULN, upper limit of normal. both considered unrelated to trilaciclib HR, hazard ratio; OS, overall survival; PFS, progression-free survival. Copies of this poster obtained through QR (Quick Response) and/or text key codes are for personal use only and may not be reproduced without written permission of the authors

CONFLICT OF INTERESTS DD: research funding from AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly, ER Squibb & Sons, G1 Therapeutics, Genentech, Novartis, Pfi zer, and Roche; DS: research funding from Genentech/Roche and G1 Therapeutics; advisory board for Genentech/Roche; JJ: research grant from AstraZeneca; advisory board for AstraZeneca, ESMO Congress 2019 • September 27 ‒ October 1, 2019 • Barcelona, Spain Boehringer Ingelheim, and MSD; LH: research funding, 1-time consulting fee, and travel expenses from G1 Therapeutics; KK: honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Intellect Pharma, Merck, MSD, Novartis, Pfi zer, Roche, and Servier; travel/accommodation/expenses from Amgen, Astellas, AstraZeneca, Eli Lilly, MSD, Pfi zer, and Roche; advisory board for AstraZeneca, Astellas, Roche, and Servier; ZY, SW, RM, SRM, JMA: employees of G1 Therapeutics; VK, IB, OI, AD, SR, TM, IK, AM, JG: no confl icts of interest

G1002-19F_ESMO_trila_SCLC_Poster_v1.8_10Sep2019_PRESS.indd 1 20/09/2019 17:22:52