Lung cancer (NSCLC) development updates

• Durvalumab + cCRT: stage III unresectable la NSCLC – P3 PACIFIC-2 (NCT03519971)
• anticipated data readout in H2 2023, anticipated a subsequent regulatory filing in 2024 
• Durvalumab +/- tremelimumab +/- chemo: 1L mNSCLC – P3 POSEIDON (NCT03164616)
• durvalumab +/- tremelimumab received US and JP approvals in Q4’22, and is anticipating EU regulatory decision in H1 2023. Planned launch is underway in NSCLC following approvals
• Durvalumab + chemo: 1L PD-L1-high adv NSCLC – P3 PEARL (NCT03003962)
• trial has been discontinued, following AstraZeneca’s recent announcement that the trial failed to meet its primary endpoint of OS
• Durvalumab (consolidation therapy): unresectable la/NSCLC not progressed after chemo – P3 PACIFIC-5 (NCT03706690)
• anticipated data readout and subsequent regulatory acceptance in China in H1 2023

• Datopotamab deruxtecan (Dato-DXd; TROP2 ADC): 2L/3L prior CPI and chemo, adv/mNSCLC - P3 TROPION-Lung01 (NCT04656652)
  • anticipated readout for H1 2023 and subsequent regulatory filing in H1 2023
• Datopotamab deruxtecan (Dato-DXd; TROP2 ADC) + durvalumab + chemo: 1L la/mNSCLC w/o AGAs – P3 AVANZAR (NCT05687266)
  • anticipated TROPION-Lung01 data to further inform and support P3 AVANZAR developments, especially around the TROP2+ biomarker analysis
• new trial was initiated in 2022, noting this is the first trial with a TROP2 biomarker in the primary analysis (first posted on clinicaltrials.gov in January 2023)
• anticipated data readout with a subsequent regulatory acceptance in >2024
• Datopotamab deruxtecan (Dato-DXd; TROP2 ADC) + pembro +/chemo: adv/mNSCLC - P1 TROPION-Lung02 (NCT04526691)
• anticipated data readout in 2024

• anticipated data readouts in >2024 from the following clinical trials:
• Datopotamab deruxtecan (Dato-DXd; TROP2 ADC) + durvalumab +/- chemo: adv/mNSCLC – P1b TROPION-Lung04 (NCT04612751)
• Datopotamab deruxtecan (Dato-DXd; TROP2 ADC) + pembrolizumab: 1L, PD-L1 ≥50% adv/mNSCLC w/o AGAs– P3 TROPION-Lung08 (NCT05215340)
• Datopotamab deruxtecan (Dato-DXd; TROP2 ADC) + pembro +/- chemo: 1L PD-L1 TPS <50% nsq adv / mNSCLC w/o AGAs – P3 TROPION-Lung07 (NCT05555732)

• MEDI5752 (PD1-CTLA4 bi-specific antibody) +/- chemo: advanced solid tumors, including NSCLC – P1b/2 (NCT03530397)
• accelerated development in CTLA-4-sensitive tumor types and longer follow-up data for 750mg dose supports the transition to late-stage
• plans to initiate five phase 3 trials in 2023 across key tumor types, including NSCLC
• anticipated data readout in 2024

• Ceralasertib (ATR) + Durvalumab: 2L/3L+ adv/mNSCLC w/o AGAs – P3 LATIFY (NCT05450692)
• anticipated data readout and a subsequent regulatory decision in >2024 

• AZD2936/ rilvegostomig (anti-TIGIT/anti-PD-1 bispecific mAb): adv./mNSCLC – P1/2 ARTEMIDE-01 (NCT04995523)
• the first patient was dosed in the phase 2 part of the trial
• plans to initiate a P3 trial in 2023
• anticipated data readout in 2024

• Pembrolizumab: Resected stage IB – IIIA NSCLC, adjuvant – P3 KEYNOTE-091 / PEARLS (NCT02504372)

• FDA approval of Keytruda in stage IB-IIIA adjuvant NSCLC following resection and platinum-based chemo, based on KEYNOTE-091, and expect this  launch in earlier stage NSCLC indication to add to overall growth of pembro sales in the US
• adjuvant pembro is under EU review for NSCLC
• Pembro is the only IO therapy available for patients with stage IB disease and regardless of PD-L1 expression
• it is expected a “slower ramp-up” as there is need to drive earlier diagnosis
• estimated the vast majority of the lung cancer diagnosis are in the metastatic setting and that of the 120,000 patients diagnosed with early-stage NSCLC, only 25% undergo surgery (leaving approximatively 30,000 patients as the addressable population for adjuvant pembro)
• However, only half of the 30,000 patients undergoing surgery have historically received adjuvant chemo or IO (atezolizumab)
• Moving forwards, commercial strategy is likely to focus on increasing screening for diagnosis and driving more adherence to guidelines to ensure the maximum early-stage NSCLC patients receive adj. pembro 

• 3 key trials focusing on early-stage NSCLC adding to the approval of KEYNOTE-091:

• Pembrolizumab + platinum doublet chemotherapy: neoadjuvant followed by adjuvant therapy, resectable stage II-IIIB NSCLC - P3 KEYNOTE-671 (NCT03425643)
• Pembrolizumab: patients undergoing stereotactic body radiotherapy with unresected stage I or II NSCLC - P3 KEYNOTE-867 (NCT03924869)
• Pembrolizumab +/- maintenance Olaparib: 1L metastatic sqNSCLC - P3 KEYLINK-008 (NCT03976362)

• Pembrolizumab subcutaneous: 1L mNSCLC– P3 MK-3475-A86 (NCT04956692)

• SC pembro in NSCLC is one of core elements in the goal to increase pembro uptake in the early-stage NSCLC setting

• More P3 studies evaluating SC pembro will be initiated this year in order to investigate further options of treatment cycles 

• Atezolizumab + chemo: stage II-IIIB resectable NSCLC, periadjuvant – P3 IMpower030 (NCT03456063)

• readout and EU/US regulatory filing expected by 2023 -> 2024 (previously anticipated in 2023 according to Roche’s Q3 earnings report)

• Atezolizumab SC (subcutaneous): 2L NSCLC – P1b/3 IMscin001 (NCT03735121)

• announced positive P3 results, where subcutaneous (SC) atezo performed comparably to IV atezo formulation without compromising safety and efficacy in 2L NSCLC
• Roche has filed for EU/US regulatory approval for atezo SC in all approved atezo indications in 2022

• Atezolizumab + cabozantinib: 2L locally advanced or metastatic NSCLC – P3 CONTACT-01 (NCT04471428) - trial DISCONTINUED
  • This follow Exelixis’ previous announcement that cabo + atezo failed to meet its 1EP of OS at final analysis in December 2022

• Tiragolumab + atezo: 1L PD-L1≥50% NSCLC – P3 SKYSCRAPER-01 (NCT04294810)

• anticipated data readout in 2H 2023; if positive, this upcoming OS interim analysis will likely lead to a regulatory filing in the EU and US

• Tiragolumab + atezo: stage III unresectable 1L NSCLC – P3 SKYSCRAPER-03 (NCT04513925)

• anticipated EU/US regulatory filing in 2024

• Tiragolumab + atezo + chemo: 1L non-squamous NSCLC – P3 SKYSCRAPER-06 (NCT04619797)

• anticipated EU/US regulatory filing in ≥2025

• Tiragolumab + atezo +/- chemo: untreated stage II-IIIB NSCLC, neoadjuvant and adjuvant – P2 SKYSCRAPER-05 (NCT04832854)

• anticipated EU/US regulatory filing in ≥2025

Sources: AstraZeneca Q4 & FY22 earnings (webcast, press release, presentation, and clinical trials appendix), Merck Q4’&FY22 earnings (webcast, press release, presentation, and financial highlights);

Roche Q4/FY’22 earnings (webcast, press release, presentation, and investors’ update).