Background

Aldesleukin (IL-2), at high doses in repeat cycles, is approved as monotherapy for patients (pts) with metastatic melanoma. Its limited efficacy is mediated through endogenous T cell activation, which also contributes to considerable toxicity (Rosenberg NEJM 1988). Lifileucel, a one-time investigational TIL cell therapy, showed a 31% IRC-assessed objective response rate (ORR) in 153 pts with advanced melanoma who progressed after immune checkpoint inhibitors and targeted therapy (if BRAF mutation positive) in the phase 2 C-144-01 trial (Sarnaik SITC 2022) using abbreviated high-dose IL-2 (≤6 doses) with 79% lower potential maximum cumulative exposure than monotherapy. Prior studies found no association between IL-2 dosing and TIL cell therapy efficacy (Goff JCO 2016, Seitter CCR 2021). This post hoc analysis explores the association between number of IL-2 doses and clinical outcomes of lifileucel.

Methods

Pts with advanced melanoma received cyclophosphamide and fludarabine (NMA-LD, Day –7 to –1), a single lifileucel infusion (Day 0), and ≤6 IL-2 doses (600,000 IU/kg) every 8–12 h (Day 0–4). Per protocol, IL-2 was discontinued based on physiologic tolerance. The association between number of IL-2 doses administered and ORR (RECIST v1.1 per IRC) and duration of response (DOR) was explored.

Results

In 153 pts who received lifileucel, median number of IL-2 doses was 6 (1–2 doses: n=16; 3–4 doses: n=26; 5–6 doses: n=109; 2 pts did not receive IL-2). All pts developed G3/4 lymphopenia (per lab values) after NMA-LD (Day 0–4). ORR to lifileucel was 38%, 31%, and 31% in pts receiving 1–2, 3–4, and 5–6 doses, respectively (p=0.87); 67%, 75%, and 47% of responders had DOR ≥12 mo (Cox regression p=0.39). ORR was 40% in 5 pts who progressed after prior high-dose IL-2 monotherapy.

Conclusions

Lifileucel ORR and DOR were not associated with number of IL-2 doses administered. Pts with disease refractory to prior IL-2 monotherapy derived benefit from lifileucel. Presence of G3/4 lymphopenia in all pts at time of IL-2 administration argues against a direct antineoplastic effect of abbreviated IL-2 dosing as part of the lifileucel regimen.

Clinical trial identification

NCT02360579.

Editorial acknowledgement

Medical writing support was provided by Jayasri Srinivasan and Swati Ghatpande of Second City Science, a Vaniam Group Company.

Legal entity responsible for the study

Iovance Biotherapeutics, Inc.

Funding

Iovance Biotherapeutics, Inc.

Disclosure

J.C. Hassel: Financial Interests, Personal, Other, Honoraria: Almirall, Amgen, Novartis, Roche; Financial Interests, Personal, Other, Honoraria, Research Funding: BMS, Sanofi; Financial Interests, Personal, Other, Honoraria, Consulting Or Advisory Role: GSK, MSD, Pierre Fabre; Financial Interests, Personal, Other, Honoraria, Research Funding, Consulting Or Advisory Role, Travel, Accommodations, Expenses: Sunpharma. A. Sarnaik: Financial Interests, Personal, Other, Research Funding, Patents, Royalties, Other Intellectual Property: Provectus; Financial Interests, Personal, Other, Consulting Or Advisory Role, Research Funding, Travel, Accommodations, Expenses, Patents, Royalties, Other Intellectual Property: Iovance; Financial Interests, Personal, Other, Honoraria: Physicians' Educational Resource, Medscape, Medstar Health; Financial Interests, Personal, Other, Consulting Or Advisory Role: Guidepoint, Defined Health, Huron Consulting Group, Keyquest, Istari, Gerson Lehrman Group. J. Chesney: Financial Interests, Personal, Other, Consulting Or Advisory Role, Research Funding: Amgen; Financial Interests, Personal, Other, Research Funding: Replimune, Iovance, FATE. T. Medina: Financial Interests, Personal, Advisory Role, consulting: Pfizer, Taiga, Merck, Bristol Myers Squibb, Iovance, Moderna, Nektar, Regeneron, Exicure, Checkmate, BioAtla, Xencor, Replimune, Day One Pharmaceutical. O. Hamid: Financial Interests, Personal, Other, consulting or advisory role, speaker bureau: BMS, Sanofi Regeneron, Novartis, Pfizer; Financial Interests, Personal, Other, speaker bureau: Novartis, Pfizer; Financial Interests, Personal, Other, consulting or advisory role: Aduro, Akeso, Alkermes, Beigene, Bioatla, Roche Genentech, GlaxoSmithKine, Immunocore, Idera, Incyte, InstilBio, Iovance, Janssen, Merck, Nextcure, Seattle Genetics, Tempus, Zelluna; Financial Interests, Institutional, Other, contracted research (for institution): Arcus, Aduro, Akeso, Amgen, Bioatla, BMS, CytomX, Exelixis, Roche Genentech, GlaxoSmithKline, Immunocore, Idera, Incyte, Iovance, Merck, Moderna, Merck-Serono, NextCure, Novartis, Pfizer, Rubius, Sanofi/Regeneron, Seattle Genetics, Taiga, Torque, Zelluna. S. Thomas: Financial Interests, Personal, Other, Research Funding, Consulting Or Advisory Role, Travel, Accommodations, Expenses, Honoraria, Speaker’s Bureau: BMS, Merck, Pfizer, Ipsen, Amgen, Genentech, Foundation One. M. Wermke: Financial Interests, Personal, Other, Honoraria, Consulting or Advisory Role: Novartis, Lilly; Financial Interests, Personal, Other, Honoraria, Consulting or Advisory Role, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Honoraria, Consulting or Advisory Role, Research Funding, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Consulting or Advisory Role, Travel, Accommodations, Expenses: Bristol Myers Squibb, GEMoaB, AstraZeneca, Amgen; Financial Interests, Personal, Other, Consulting or Advisory Role: Cellex GmbH, Boehringer Ingelheim, ISA Pharmaceuticals, MSD, Immatics. E. Domingo-Musibay: Financial Interests, Personal, Other, Speaker’s Bureau, Consulting Or Advisory Role: Regeneron; Financial Interests, Personal, Other, Honoraria: Castle Biosciences; Financial Interests, Personal, Other, Research Funding: Clinigen. J.M. Kirkwood: Financial Interests, Personal, Other, Consulting/SAB: Amgen, Inc., Ankyra Therapeutics, Applied Clinical Intelligence, Llc, Axio Research, Llc, Becker Pharmaceutical Consulting, Bristol Myers Squibb, Cancer Network, Checkmate Pharmaceuticals, DermTech, Fenix Group International, Harbour BioMed, Immunocore Llc, Iovance Biotherapeutics, IQVIA, Istari Oncology, Merck, Natera, Inc., Novartis Pharmaceuticals, OncoCyte Corporation, OncoSec Medical Inc., Pfizer, Inc., Replimune, Inc., Scopus BioPharma, Inc., SR One Capital Management, LP, Takeda Development Center Americas, Inc., Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Other, Research Trial Support to Institution: Amgen, Inc., Bristol Myers Squibb, Checkmate Pharmaceuticals, Harbour BioMed, Immvira Pharma Co., Immunocore Llc, Iovance Biotherapeutics, Novartis Pharmaceuticals, Takeda, Verastem, Inc. J. Larkin: Financial Interests, Personal, Other, Honoraria: Eisai, Novartis, Incyte, Merck, touchIME, touchEXPERTS, Royalo Collge of Physicians, Cambridge Healthcare Research, Royal College of General Practitioners, VJOncology, Agence Unik, BMS; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pierre Fabre, Roche, GSK; Financial Interests, Personal, Other, Consulting Or Advisory Role: iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm, Incyte ; Financial Interests, Personal, Other, Research Funding: BMS, MSD, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, Aveo. J.S. Weber: Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: Named on CTLA4 biomarker patent and a TIL growth patent by Moffitt Cancer Center and a PD-1 biomarker patent by Biodesix; Financial Interests, Personal, Stocks/Shares: Biond, Instil Bio, OncoC4, Evaxion; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS; Financial Interests, Personal, Other, Honoraria, Consulting Or Advisory Role: BMS, Merck, GSK, Pfizer, Sellas, Biond, OncoC4, ImCheck, Genentech, AstraZeneca, Regeneron, Instil Bio, Iovance, Evaxion, Ultimovacs; Financial Interests, Personal, Other, Research Funding: BMS, Moderna, Merck, Incyte, Genentech. A.M. Arance Fernandez: Financial Interests, Personal, Invited Speaker, Speaker’s Bureau: BMS, Roche, Novartis, Pierre Fabre, MSD, Merck, Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: BMS, MSD, Novartis, Pierre Fabre; Financial Interests, Personal, Other, Consulting Or Advisory Role: BMS, Roche, Novartis, Pierre Fabre, MSD, Merck, Sanofi; Financial Interests, Personal, Other, Research Funding: Pierre Fabre, Novartis, Roche, BMS, MSD, Merck, Sanofi. J.F. Rodriguez: Financial Interests, Personal, Other, Employment: HM Hospitales; Financial Interests, Personal, Other, Advisory boards and Consul∖ng: BMS, Amgen, Novartis, Rainier, Janssen, Pierre-Fabre; Financial Interests, Personal, Other, Speaker honoraria: Roche, BMS, Novartis, MSD, Janssen, Pfizer, AstraZeneca, EUSA-Pharma, Astellas, Bayer; Financial Interests, Personal, Other, Travel, accommodations, expenses: Astellas, Novartis, Roche, BMS, Pfizer, MSD, Pierre-Fabre; Financial Interests, Personal, Other, Corporate-sponsored research: AstraZeneca, BMS, Amgen, Roche, Novartis, MSD, Janssen, Pfizer, Astellas, GSK, PharmaMar, Ipsen, Tesaro, AbbVie, Aprea Therapeutics, Eisai, Bayer, Merck. I. Thomas: Financial Interests, Personal, Other, Congress and travel expenses: AbbVie, Roche, Sanofi; Financial Interests, Personal, Other, Honoria and travel expenses for talks: Pierre Fabre; Financial Interests, Personal, Other, Honoraria for advisory board: BMS; Financial Interests, Institutional, Other, Research funds (ins]tu]onal): BMS, Pfizer, MSD, Amgen, Argn-X, Leo, Novartis, UCB, 4SC, AstraZeneca, Biontech, Genentech, Roche, Biotech, Curevac, Huya, Incyte, Idera, Iovance, Infla-Rx, Cerpass, Kartos, Nektar, Philogen, Pierre Fabre, Regeneron, Replimune, Sanofi. P.G. Corrie: Financial Interests, Personal, Other, advisory board and speaker honoraria: BMS, MSD, Pierre Fabre, Novartis; Financial Interests, Personal, Other, consultancy: Microbiotica; Financial Interests, Personal, Other, travel & accommodation: MSD; Financial Interests, Institutional, Other, research funding to institution: Pierre Fabre, MSD. V. Gontcharova: Financial Interests, Personal, Other, Current Employment, Current Equity Holder in publicly-traded company, Travel, Accommodations, Expenses (paid by any for-profit health care company): Iovance Biotherapeutics; Financial Interests, Personal, Other, Current Equity Holder in publicly-traded company: Gilead, Meta, Intel. X. Wu, W. Shi: Financial Interests, Personal, Other, employment with and stock or other ownership: Iovance Biotherapeutics. H. Kluger: Financial Interests, Personal, Other, Consulting Or Advisory Role: Bristol Myers Squibb, Clinigen, Shionogi, Chemocentryx, Calithera, Signatero, Gigagen, GI reviewers, Merck; Financial Interests, Personal, Other, Research Funding: Apexigen, Bristol Myers Squibb, Merck.

Background

Development of novel treatment options is essential for patients with metastatic melanoma (MM), as about half derive no durable benefit upon first-line treatment. Adoptive cell therapy with TIL has shown encouraging results in a recently completed multicenter phase 3 trial evaluating TIL in MM patients (NCT02278887); 39 (49%) patients showed a response (complete or partial) and 2 (3%) patients were not evaluable for response. Resection of a melanoma lesion (≥2-3cm) was required for the ex vivo outgrowth and expansion of TIL. However, the impact of location and size of metastasectomy used for TIL production on response is yet unknown.

Methods

Location and size of metastasectomy used for TIL production in relation to clinical response were evaluated in patients with unresectable stage IIIC-IV MM treated with TIL in a recently completed phase 3 trial. Regression analyses and corresponding Likelihood Ratio- and F-tests were performed to test statistical significance.

Results

Manufacturing of TIL was successful in 82/83 (98.8%) patients for whom production was started. In total, 80 patients were treated with a median number of 40.9x10⁹ TIL (range 4.9 – 110.4), of which 36 (45%), 34 (42.5%) and 10 (12.5%) underwent resection of a lymph node, (sub)cutaneous or visceral metastasis for TIL manufacturing, respectively. Visceral metastases included lung (n=6), liver (n=1), adrenal gland (n=1), small intestine (n=1) and spleen (n=1). Median time from randomization to metastasectomy was 10.3 days (range -14.5 – 22.5). In 10 (12.5%) patients, a second metastasectomy was performed due to initial insufficient TIL outgrowth. Location of metastasectomy had no influence on clinical response (p=0.949) or on the number of cells produced (p=0.540). In 50 (62.5%) patients 1 lesion of ≥ 2-3cm and in 30 (37.5%) patients >1 lesion was resected to obtain the required ≥ 2-3cm, with no differences in resulting cell numbers (p=0.115).

Conclusions

A high success rate of TIL manufacturing was observed for MM patients treated with TIL in a recently completed multicenter phase 3 trial. Location and size of metastasectomy had no impact on clinical response or cell numbers, making TIL a robust treatment option.

Clinical trial identification

NCT02278887.

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

The Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the Dutch Ministry of Health, Stichting Avento, AVL Foundation, Copenhagen University Hospital, Herlev, the Danish Cancer Society and Capital Region of Denmark Research Foundation.

Disclosure

T. Holz Borch: Financial Interests, Personal, Invited Speaker: BMS. J.H. van den Berg: Financial Interests, Institutional, Research Grant: NEON therapeutics, BMS, MedImmune. W. Van Houdt: Financial Interests, Institutional, Invited Speaker: Amgen, BMS; Financial Interests, Institutional, Advisory Board: Belpharma; Financial Interests, Institutional, Expert Testimony: Sanofi, MSD; Financial Interests, Personal, Other, travel grant: Novartis. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Novartis, MSD - Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC, Provectus; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS, MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Personal, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Personal, Member: ASCO, AACR, SITC; Other, Personal, Other, Editor-in-Chief IOTECH: ESMO; Other, Personal, Other, Editorial Board ESMO Open: ESMO; Other, Personal, Other, Editorial Board: Kidney Cancer. All other authors have declared no conflicts of interest.

Background

The stimulation of antitumor CD4 T helper response represents a critical requirement for therapeutic cancer vaccine effectiveness. In this context, we developed a Th1-inducer anticancer peptide vaccine derived from telomerase called UCPVax (Dosset et al. Clin Can Res 2012). The safety and efficacy of UCPVax therapeutic vaccination were recently reported in metastatic non-small cell lung cancer (NSCLC) phase I/II trial (Adotévi et al., J Clin Oncol 2022, NCT02818426). Here, we described the immunological responses promoted by UCPVax.

Methods

Immune monitoring was performed in 52 patients with refractory metastatic NSCLC previously vaccinated with three doses of UCPVax for six times (one per week) followed by boost every two months for one year. Blood samples were collected before and at different times after vaccination. Vaccine-specific CD4 T cell responses and epitope spreading were evaluated by IFN-γ ELISPOT assay. MHC class II pentamer staining and intracellular cytokine secretion assay were used for the assessment of phenotype function and polarization of antigen specific CD4 T cells. Vaccine induced antibody response was measured by ELISA.

Results

Seventy % of patients mounted strong UCP-specific CD4 T cells after vaccination regardless the dose level. UCPVax induced de novo and strong UCP-specific CD4 T-cell response and the intensity of the response increased according to the number of vaccinations. The UCP-specific CD4 T cells were effector memory phenotype, showed cytotoxic potential and (IFN-γ,TNF-a, IL-2)⁺ Th1 polarization which were maintained in long-term responders. Increased level of antibody response against UCP was found in 45% of patients which was correlated to the number of UCP-CD4 T cells. Furthermore, UCPVax induced epitope spread responses against various tumor antigens in most of patients analyzed. Finally, patients displayed polyfunctional anti-UCP CD4 response and epitope spreading had a better survival.

Conclusions

UCPVax vaccination promotes highly functional and long-lasting tumor specific CD4 T cell responses associated with the improvement of patients’ survival.

Clinical trial identification

NCT02818426.

Legal entity responsible for the study

O. Adotevi.

Funding

National Cancer Institute INCa France PHRC program.

Disclosure

O. Adotevi: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Non-Financial Interests, Personal, Principal Investigator: MSD. V. Westeel: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Amgen, Lilly, MSD, BMS. C. Borg: Financial Interests, Personal, Advisory Role: MSD Oncology, Roche; Financial Interests, Institutional, Sponsor/Funding: Bayer. All other authors have declared no conflicts of interest.

Background

We profiled clinical and biomarker data from this prospective, multicenter, phase II study evaluating the efficacy and safety of NA nivo with or without platinum-doublet chemotherapy based on PD-L1 status (NCT04015778).

Methods

Patients (pts) had resectable clinical stage IIA-IIIB (AJCC 8th) NSCLC and ECOG PS 0/1 with no EGFR/ALK variations. Pts received mono-nivo 360mg treatment (tx) for ≤3 cycles q3w or nivo 360mg + nab-paclitaxel 185mg/m2 (d1, d8) + carboplatin AUC5 for ≤3 cycles q3w based on PD-L1 status. Primary endpoint was major pathological response (MPR: ≤10% viable tumor cells). Key secondary endpoints included pathologic complete response (pCR), objective response rate (ORR, RECIST v1.1), adverse events (AEs) including treatment-related (TRAE) and immune-related (irAE). We correlated PD-L1 status and perioperative ctDNA presence with pCR and event-free survival (EFS).

Results

From 08/08/2019 to 08/16/2021 52 pts were accrued and 46 had surgery (surg outcome in the table). The pre-surg ORR was 51.9% (27/52) with 2 CR. 25/46 (54.3%) achieved MPR of which 13 (28.3%) were pCR. In PD-L1 ≥ 50% group mono-nivo achieved 18.2% MPR while chemoimmunotherapy achieved 80%. AEs occurred in all pts during NA tx, including irAEs in 36/52 (69.2%) and 3 pts discontinued NA tx. 45 (97.8%) pts had sufficient tissue for tumor-informed MRD. MRD was detected in 84.4% in pre-NA (n=38), 91.1% in post-NA (n=41) and 80.0% in post-surg samples (n=36). Significant ctDNA clearance post-NA was seen in pts with pCR vs non- pCR (OR=8.56, 95% CI: 1.22-Inf, p=0.03). With a median follow-up of 25.1 months (95% CI: 22.4-27.7m), 2yr-EFS rate for pts with MRD– (both post-NA and -surg) vs. MRD+ (either post-NA or -surg) was 86.6% vs 47.3% (HR, 0.20; 95% CI: 0.04, 0.94; p=0.02). Table: LBA2

Conclusions

We prefer chemoimmunotherapy as neoadjuvant treatment regardless of PD-L1 expression. ctDNA clearance would be a predictor of favorable pathological and survival outcomes.

Clinical trial identification

NCT04015778.

Legal entity responsible for the study

Chinese Thoracic Oncology Group, CTONG.

Funding

Bristol Myers Squibb.

Disclosure

W. Zhong: Non-Financial Interests, Personal, Board Member in the Educational Committee (mainly participated in educational event organization): International Association for the Study of Lung Cancer (IASLC). Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merck, MSD, Pfizer, Roche, Sanofi, Yunhan; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). All other authors have declared no conflicts of interest.

Background

Penpulimab is a novel humanized IgG1 mAb that blocks PD-1 binding to PD-L1, engineered to eliminate FcγR binding and ADCC/ADCP completely.

Methods

AK105-302 is a 1:1 randomized, double-blind, placebo-controlled, multicenter, phase III trial to compare penpulimab or placebo plus carboplatin and paclitaxel as first-line treatment for locally advanced or metastatic squamous NSCLC. The stratification factors included PD-L1 and gender. Eligible pts were randomized 1:1 to receive penpulimab 200 mg or placebo plus chemotherapy every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy until disease progression or 24 months, subjects in placebo group may choose to cross over to open-label penpulimab monotherapy for up to 24 months. The primary endpoints were PFS in the ITT population and in the PD-L1-positive population (TPS of PD-L1≥1%), assessed by an IRRC. The secondary endpoints were OS, ORR, DoR, DCR and TTR.

Results

175 pts were assigned to penpulimab plus chemotherapy (P+C) and 175 to placebo plus chemotherapy (C). At data cutoff (Jun 1, 2022), the median follow-up was 23.56m. The mPFS by IRRC was significantly longer with P+C than with C (7.6m vs. 4.2m; HR 0.44, 95%CI: 0.34-0.56; p < 0.0001), 12m-PFS rate (37.1% vs. 9.2%) and 24m-PFS rate (23.8% vs. 5.9%) were significantly higher in P+C than C. In the PD-L1-positive population, the mPFS by IRRC was also significantly longer with P+C than with C (8.1m vs. 4.2m; HR 0.37, 95%CI: 0.27-0.51; p < 0.0001). The mOS of P+C was not reached, but the benefit trend was obvious (NR vs. 19.8m; HR 0.55, 95%CI: 0.40-0.75; p = 0.0002), 24m-OS rate (61.1% vs. 41.6%) were significantly higher in P+C than C. ORR by IRRC was 71.4% in P+C and 44.0% in C. Treatment with P+C was associated with more durable response (mDoR by IRRC: 8.25m vs 2.96m) than C. Grade ≥3 TRAEs occurred in 63.6% (P+C) vs. 62.9% (C). Serious TRAEs occurred in 28.3% (P+C) vs. 26.9% (C). TRAEs led to treatment discontinuation were 5.2% in P+C and 3.4% in C.

Conclusions

These positive data will support penpulimab plus chemotherapy may be a promising and safe first-line treatment for locally advanced or metastatic squamous NSCLC.

Clinical trial identification

NCT03866993.

Legal entity responsible for the study

Chai Tai Tianqing Pharmceutical Group Co, Ltd. Akeso Tiancheng, Inc.

Funding

Chai Tai Tianqing Pharmceutical Group Co,Ltd. Akeso Tiancheng, Inc.

Disclosure

All authors have declared no conflicts of interest.

Background

Cemi (anti-PD-1) used as monotherapy has been shown to improve overall survival (OS) vs chemo in patients (pts) with advanced NSCLC, no EGFR, ALK or ROS1 aberrations, and PD-L1 expression in ≥50% of tumor cells. Since the benefit of PD-(L)1 blockade decreases with decreased PD-L1 expression, combination therapies are required for tumors with low PD-L1. Both chemotherapy and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have been shown to augment the effects of anti–PD-1 in pts with advanced NSCLC. The addition of a reduced course of chemo and CTLA-4 to anti-PD1 could provide an additional benefit in pts with PD-L1 expression <50%.

Methods

In EMPOWER-Lung 3 part 1, 323 pts with PD-L1 expression of <50% were randomized (1:1:1) to: standard platinum-based doublet chemo for 4 cycles (StC), cemi 350 mg once every 3 weeks (Q3W) for up to 108 weeks + standard chemo, or cemi 350 mg Q3W for up to 108 weeks + reduced chemo for 2 cycles + ipi 50 mg Q6W for up to 4 cycles (CIC). The primary endpoint was OS. Secondary endpoints included progression free survival (PFS), objective response rate (ORR), patient-reported outcomes, and safety. Part 1 was stopped early due to reprioritization to standard chemo+cemi for NSCLC pts regardless of PD-L1 expression and only descriptive statistical analyses were done.

Results

49% of pts in each group had <1% expression of PD-L1. At a median (med) follow-up of 35.5 months (m), med OS was 20.1m (13.7, 28.3) for CIC pts (N=109) vs 13.9 (10.0, 17.7) for StC pts (N=106), with a hazard ratio (HR) of 0.615 (95% confidence interval, 0.441, 0.857). Med PFS was 6.4m vs 6.3m with HR of 0.813 (0.596, 1.108). ORR was 35.8% and 28.3% for CIC and StC, respectively. Med duration of response was 15.9m vs 6.3m. Safety profile was generally consistent with the known safety profile for cemi, chemo, and ipi. Grade ≥3 treatment emergent adverse events (TEAEs) were observed in 43.1% of CIC pts and 42.7% of StC pts, TEAEs resulting in discontinuation of study treatment or death observed in 4.6% vs 0%, and in 4.6% vs 4.9%, of CIC and StC pts respectively.

Conclusions

In this descriptive analysis, the addition of cemi and ipi to a reduced course of chemo led to a meaningful OS benefit in pts with PD-L1 <50%.

Clinical trial identification

NCT03409614.

Editorial acknowledgement

Medical writing support was provided by Osnat Ben-Shahar PhD of Regeneron Pharmaceuticals, Inc.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc. and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

K.D. Penkov: Financial Interests, Personal, Advisory Board: Nektar terapeutics; Financial Interests, Personal and Institutional, Invited Speaker: AbbVie, AstraZeneca, Pfizer, Jounce Terapeutics, Polyphor, GSK, Mabscale, Biocad, Sanofi, Novartis, Regenegon pharmaciutical. E. Kalinka: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, AstraZeneca, Roche, Gilead; Financial Interests, Personal, Writing Engagements: Bristol Myers Squibb, AstraZeneca, Nektar; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, AstraZeneca, Gilead; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb, MSD, AstraZeneca, Roche, Gilead, Nektar. C. Gessner: Financial Interests, Personal, Other: GlaxoSmithKline, Pfizer, AstraZeneca, Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Berlin-Chemie, Chiesi , Boehringer Ingelheim, Sanofi; Financial Interests, Personal, Advisory Board: GlaxoSmithKline , Pfizer, AstraZeneca, Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme , Berlin-Chemie, Chiesi, Boehringer Ingelheim, Sanofi. R. Passalacqua: Financial Interests, Institutional, Research Grant: Amgen, Pierre-Fabre; Financial Interests, Personal, Advisory Board: Amgen, Pierre-Fabre; Financial Interests, Personal, Other: Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Sanofi-Aventis , Roche, MSD, Regeneron. M.C. Garassino: Financial Interests, Personal, Advisory Board: Eli Lilly, SeaGen International GmbH, Eli Lilly, Daiichi Sankyo, Incyte, GlaxoSmithKline, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, AstraZeneca and Daiichi Sankyo Oncology Teams, Roche, Daiichi Sankyo, Mirati Therapeutics, Inc, Daiichi Sankyo/AstraZeneca, AstraZeneca Poland, Daiichi Sankyo, Inc., MSD, Eli Lilly, Pfizer, Astrazenca/MedImmune, Sanofi Genzyme corporation, Sanofi / Prex, Regeneron Pharmaceuticals, Eli Lilly, Mirati Therapeutics, Inc.; Financial Interests, Personal, Invited Speaker: WebMD, WebMD Oncology/Takeda, MSD, MSD Italia, Srl, GrupoPacifico-Secretaria Técnica ICAPEM/AstraZeneca, S.O.S S.r.l, Medscape, ecancer; Financial Interests, Personal, Invited Speaker, Global Experts Meeting: AstraZeneca; Financial Interests, Personal, Other, AstraZeneca Spain: Invitation to a lung cancer investigator meeting: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Board Nazionale Brigatinib: Takeda; Financial Interests, Personal, Other, PACIFIC-R Global Scientific Committee: AstraZeneca; Financial Interests, Personal, Other, Steering Committee member and Co-chair at the AstraZeneca Lung Cancer Summit 2019: AstraZeneca; Financial Interests, Personal, Other, MK-3475 KN671 Steering Committee: MSD; Financial Interests, Personal, Other, Pacific 6 International Coordinating Investigator: AstraZeneca; Financial Interests, Personal, Other, Jannesen Scientific Advisory Board and Therapeutic Area Steering Committee Meeting on Lung Cancer: Janssen; Financial Interests, Personal, Expert Testimony: AstraZeneca UK; Financial Interests, Personal, Other, Pfizer Global Lung Cancer Educational Programme - Steering Committee: Pfizer; Financial Interests, Personal, Other, Seattle Genetics Lung Cancer Platform Study: Seattle Genetics; Financial Interests, Personal, Other, GSK Lung Cancer Global Council: GSK; Financial Interests, Personal, Other, PACIFIC-R Scientific Committee: AstraZeneca UK; Financial Interests, Personal, Other, GSK-Garassino- ZEAL Steering Committee 2020-23: GSK; Financial Interests, Personal, Invited Speaker, Member of the MK-3475 KN671 Steering Committee (Keynote-671): MSD; Financial Interests, Personal, Invited Speaker, Coordinating investigator for the MK-3475 Keynote 189: MSD; Financial Interests, Personal and Institutional, Invited Speaker, Pacific 6 Steering Committee and International Coordinating Investigator: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Steering Committee ML41118 Roche: Roche; Financial Interests, Institutional, Invited Speaker, Turning Point: Bayer; Financial Interests, Institutional, Invited Speaker, A Phase 1: Janssen; Financial Interests, Institutional, Invited Speaker, Array 818-202: Pfizer; Financial Interests, Institutional, Invited Speaker, PAPILLON Study: Janssen; Financial Interests, Institutional, Invited Speaker, Phase II: Celgene Corporation, Spectrum Pharmaceuticals, Merk Serono; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker, Phase 3: Bluprint; Financial Interests, Institutional, Invited Speaker, Phase III: Amgen, GlaxoSmithkline Research & Develpoment Ltd., Novartis; Financial Interests, Institutional, Invited Speaker, Phase III - CEACAM5: Sanofi; Financial Interests, Institutional, Invited Speaker, Phase I-JNJ-61186372, a Human Bispecific EGFR and cMet Antibody: Janssen; Financial Interests, Institutional, Invited Speaker, Phase 3 Study RESILIENT: IPSEN Bioscience Inc.; Financial Interests, Institutional, Invited Speaker, Phase II - SAVANNAH: AstraZeneca S.p.A.; Financial Interests, Institutional, Invited Speaker, phase III NEOCOAST: MedImmune LCC; Financial Interests, Institutional, Invited Speaker, Phase II - coast: MedImmune LCC; Financial Interests, Institutional, Invited Speaker, Phase III - ADRIATIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Phase III (CANOPY-1): Novartis; Financial Interests, Institutional, Invited Speaker, Phase 1b: Exelixis Inc.; Financial Interests, Institutional, Invited Speaker, Phase 3-GO40241: Roche; Financial Interests, Institutional, Invited Speaker, Phase III- CASPIAN: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MK3475-091 - PEARLS: Merk; Financial Interests, Institutional, Invited Speaker, Phase III - Roche GO29431: Roche; Financial Interests, Institutional, Invited Speaker, Phase III CA209-017: BMS; Financial Interests, Institutional, Invited Speaker, Phase III - ARCTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Phase III - AURA 3: AstraZeneca AB; Financial Interests, Institutional, Invited Speaker, Phase III CA209-057: BMS; Financial Interests, Institutional, Invited Speaker, OPEL/2014/14/067: Otsuka Pharmaceutical Italy S.r.l.; Financial Interests, Institutional, Invited Speaker, Phase II - VISION: Merck KGaA; Financial Interests, Institutional, Invited Speaker, Phase III MK-3475-715: Incyte Corporation; Financial Interests, Institutional, Invited Speaker, Phase 1/2 (TRIDENT-1): Turning Point Therapeutics, Inc.; Financial Interests, Institutional, Invited Speaker, HERTHENA-Lung01: A Phase 2: Daiichi Sankyo Development Ltd.; Financial Interests, Institutional, Invited Speaker, Phase II ATLANTIC: AstraZeneca S.p.A.; Non-Financial Interests, Personal, Principal Investigator, STYLE Trial: Pfizer; Non-Financial Interests, Personal, Principal Investigator, Studio TYME: Eli Lilly; Non-Financial Interests, Personal, Principal Investigator, People: MSD; Non-Financial Interests, Personal, Principal Investigator, FAME trial: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, POST-ALK: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Bando finalizzata Mesotelioma: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, TERAVOLT: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Progetto Timoma: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, APOLLO: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Beverly: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, IND227: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, RAMES: GOIRC; Non-Financial Interests, Personal, Principal Investigator, Studio CHANCE: GOIRC; Non-Financial Interests, Personal, Principal Investigator, Creta trial: Sant'Orsola Malpighi - Bologna (Alma Mater Studiorum Università Bologna); Non-Financial Interests, Personal, Principal Investigator, MILES 5: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Leadership Role, President and Founder: Women for Oncology Italy; Non-Financial Interests, Personal, Principal Investigator, LIPI: GUSTAVE-ROUSSY PARIGI LIPI TRIAL- no profit; Non-Financial Interests, Personal, Principal Investigator: AO Spedali Civili Brescia; Non-Financial Interests, Personal, Principal Investigator, phase III trial: European Thoracic Oncology Platform (ETOP); Non-Financial Interests, Personal, Other, Member of ASCO Scientific Committee (2018-2021): ASCO; Non-Financial Interests, Personal, Leadership Role, Board member: AIOT (Associazione Italiana Oncologia Toracica); Non-Financial Interests, Personal, Member: AIOM, AIOT; Non-Financial Interests, Personal, Member, WCLC annual congress Lung Cancer Track: WCLC; Non-Financial Interests, Personal, Member, Scientific Committee: IPOP (Italian lung cancer charity), TUTOR (Italian thymic malignancies charity); Non-Financial Interests, Personal, Member, Member since 2013: EMA Scientific Advisory Group (SAG); Non-Financial Interests, Personal, Other, Scientific Programme Committee: AACR; Non-Financial Interests, Personal, Leadership Role, ESMO National Societies Committee Chair and ESMO Council Member: ESMO; Other, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Other, Personal, Other, Relationships to Disclose Travel, Accommodations, Expenses: Roche, AstraZeneca. S. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. J. Pouliot, K. McGuire, R.G. Quek, M. Kaul, G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. P. Rietschel: Financial Interests, Personal, Stocks/Shares: Regeneron; Financial Interests, Personal, Full or part-time Employment: Regeneron. All other authors have declared no conflicts of interest.

Background

This study evaluated the real-world outcomes among patients (pts) with squamous (SQ) or non-squamous cell (NSQ) advanced non-small cell lung cancer (aNSCLC) receiving either first-line (1L) immuno-oncology (IO) monotherapy or IO in combination with chemotherapy (IO+CT).

Methods

Eligible pts (age ≥18 years) were identified from the Flatiron Health database (January 2011 - March 2022) with confirmed aNSCLC (Stage III−IV) who received either 1L IO monotherapy or IO+CT on or after January 1, 2016. Pts with EGFR/ALK tumor mutations and pts with unknown histology were excluded. Overall survival (OS) and real-world progression-free survival (rwPFS) were estimated using Kaplan-Meier methods for the IO monotherapy and IO+CT cohorts. Analyses were also conducted by histology and tumor programmed death ligand 1 (PD-L1) subgroups.

Results

A total of 11,445 pts were identified, among which 4,354 (38%) received IO monotherapy and 7,091 (62%) received IO+CT. Among pts receiving IO monotherapy, median OS was 14.2 and 11.1 months for NSQ and SQ aNSCLC, respectively. Among pts receiving IO+CT, median OS was 12.1 months (NSQ) and 10.5 months (SQ). Median rwPFS was 4.7 months for pts receiving IO monotherapy, and was 5.6 months for pts receiving IO+CT. The table reports the OS and rwPFS results by histology and PD-L1 subgroups. Median OS and rwPFS were lowest in the tumor PD-L1 <1% subgroup among pts treated with IO+CT regardless of histology as well as among SQ pts receiving IO monotherapy. Table: 60MO

Survival outcomes for patients with SQ and NSQ aNSCLC receiving IO or IO+CT

Conclusions

The real-world survival estimates were generally lower than those reported in pivotal trials and it further affirms the unmet need among patients with aNSCLC, especially among those with low PD-L1 expression levels.

Legal entity responsible for the study

The authors.

Funding

Bristol Myers Squibb.

Disclosure

D.M. Waterhouse: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, AstraZeneca, Amgen, Janssen, EMD Serono, Merck; Financial Interests, Personal, Advisory Role: Jazz pharmaceuticals, Exelixis, Eisai, Pfizer, Mirati Therapeutics, Regeneron/Sanofi, Fresenius Kabi, Lilly, Sanofi, Astellas, Gilead. S. Ray: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. K.A. Betts: Financial Interests, Institutional, Other, Keith A. Betts is employee of Analysis Group Inc., which has received consultancy fees from BMS: Bristol Myers Squibb. Y. Yuan: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. L. Yin: Financial Interests, Institutional, Other, Lei Yin is employee of Analysis Group Inc., which has received consultancy fees from Bristol Myers Squibb: Bristol Myers Squibb. S. Gao: Financial Interests, Institutional, Other, Sophie Gao is employee of Analysis Group Inc., which has received consultancy fees from BMS: Bristol Myers Squibb. M. Sundar: Financial Interests, Institutional, Other, Manasvi Sundar is employee of Analysis Group Inc., which has received consultancy fees from Bristol Myers Squibb: Bristol Myers Squibb. D. Stenehjem: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Dracen Pharmaceuticals, Iterion Therapeutics, Molecular Templates, SonALAsense, Salarius Pharmaceuticals; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca, Bayer, Novartis, Jazz Pharmaceuticals.

Background

Atezo (anti–PD-L1) IV is approved in NSCLC, SCLC, triple-negative breast cancer, hepatocellular carcinoma, urothelial carcinoma and unresectable/metastatic melanoma. To reduce treatment burden and improve convenience and efficiencies in healthcare, a novel fixed-dose atezo SC co-formulated with recombinant human hyaluronidase is being developed. We report Part 2 (Phase III) of the open-label, randomized, multicentre IMscin001 study (NCT03735121) to investigate non-inferiority of drug exposure at Cycle 1 after atezo SC vs IV administration in NSCLC.

Methods

Adults with previously treated locally advanced/metastatic NSCLC (no prior cancer immunotherapy) and ECOG PS 0 or 1 were randomised 2:1 to receive 2L atezo SC (1875 mg) or IV (1200 mg) every 3 weeks. Primary endpoints: non-inferiority for Cycle 1 observed serum C_trough and model-predicted AUC_{0-21 days}; secondary endpoints: steady-state PK, safety, efficacy (PFS, ORR), patient-reported outcomes, immunogenicity.

Results

There were 247 and 124 patients in the atezo SC and IV arms, respectively (median follow-up: 4.6 mo; data cut-off: 26 Apr 2022). Median age was 64.0 years (range 27–85), 69% were male and 74% had ECOG PS 1. The lower bounds of the 90% CI of the geometric mean ratios (GMRs) for C_trough (GMR 1.05 [90% CI: 0.88, 1.24]) and AUC (GMR 0.87 [90% CI: 0.83, 0.92]) were above the predefined non-inferiority margin of 0.8. Efficacy, immunogenicity and safety were similar between arms (Table). Table: 61MO

Conclusions

Atezo SC demonstrated non-inferior exposure vs IV for both co-primary PK endpoints. Efficacy and safety were similar between arms and consistent with the known atezo IV profile; atezo immunogenicity was comparable between arms and within the historical range for atezo IV across indications. These results support atezo SC as an alternative to IV.

Clinical trial identification

NCT03735121.

Editorial acknowledgement

Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Disclosure

M. Burotto: Financial Interests, Personal, Advisory Board, Speaking at industry symposiums and consulting roles: F. Hoffmann-La Roche Ltd, MSD, BMS, AstraZeneca, Novartis; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. Z. Zvirbule: Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. A. Mochalova: Financial Interests, Personal, Stocks/Shares: Medsi Hospital Group; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. Y. Runglodvatana: Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. L.A. Herraez Baranda: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffman-La Roche Ltd. S. Liu: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. P. Chan: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. E. Shearer-Kang: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. M. Shivhare: Financial Interests, Personal, Full or part-time Employment: Roche Products Ltd; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. N. Tosti: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Funding, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffman-La Roche Ltd. J. Zanghi: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. B. Leutgeb: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd. E. Felip: Financial Interests, Personal, Advisory Role, Consultancy/Honoraria: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Ipsen, Janssen, Medical Trends, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Peervoice, Peptomyc, Pfizer, Sanofi, Springer, Takeda, Touchtime; Financial Interests, Institutional, Research Grant: *Fundación Merck Salud, Grant For Oncology Innovation and Merck, Healthcare KGaA; Non-Financial Interests, Personal, Other, Independent Member of the Board: Grifols; Non-Financial Interests, Personal, Other, Research support for third-party writing assistance for this abstract, furnished by Marcia Gamboa, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland: F. Hoffmann-La Roche Ltd.