Subcutaneous versus intravenous pembrolizumab, in combination with chemotherapy, for treatment of metastatic non-small-cell lung cancer: the phase III 3475A-D77 trial

May combine two claims.

The incidences of treatment-related AEs, grade 3-5 treatment-related AEs, and serious treatment-related AEs were similar between treatment arms.

“The incidences of treatment-related AEs, grade 3-5 treatment-related AEs, and serious treatment-related AEs were similar between treatment arms (Table 3; Supplementary Tables S5 and S6, available at https://doi.org/ 10.1016/j.annonc.2025.03.012).”

May combine two claims.

Treatment-related AEs led 8.4% of participants to discontinue pembrolizumab s.c. and 8.7% to discontinue pembrolizumab i.v.

“Treatment-related AEs led 8.4% of participants to discontinue pembrolizumab s.c. and 8.7% of participants to discontinue pembrolizumab i.v.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Of 640 participants screened, 377 were randomized to pembrolizumab s.c. plus chemotherapy (n=251) or pembrolizumab i.v. plus chemotherapy (n=126).

“Of 640 participants screened for eligibility, 377 participants at 61 global sites were randomized between 2 March 2023 and 5 January 2024 to pembrolizumab s.c.plus chemotherapy ('pembrolizumab s.c.arm', n ¼ 251) or pembrolizumab i.v.plus chemotherapy ('pembrolizumab i.v.arm', n ¼ 126) arm”

May combine two claims.

The geometric means for cycle 1 AUC 0-6 weeks and cycle 3 C trough were similar between treatment arms.

“The geometric means (95% CI) for cycle 1 AUC 0-6 weeks and cycle 3 C trough were similar between treatment arms (Table 2).”

May combine two claims.

The median PFS was 8.1 months (95% CI 6.3-8.3 months) in the pembrolizumab s.c. arm and 7.8 months (95% CI 6.2-9.7 months) in the pembrolizumab i.v. arm (HR 1.05, 95% CI 0.78-1.43).

“The median PFS was 8.1 months (95% CI 6.3-8.3 months) in the pembrolizumab s.c.arm and 7.8 months (95% CI 6.2-9.7 months) in the pembrolizumab i.v.arm (HR 1.05, 95% CI 0.78-1.43)”

Probably not a substantial claim: may not pass S3 (load-bearing).

The median follow-up from randomization to data cut-off (12 July 2024) was 9.6 months (range 6.24-16.39 months).

“The median follow-up, defined as the time from randomization to the date of data cut-off, 12 July 2024, was 9.6 months (range 6.24-16.39months).”

May combine two claims.

Pembrolizumab 790 mg s.c. q6w administration was associated with relatively higher cycle 1 C trough and steady-state AUC 0-6 weeks, and relatively lower C max in both cycles 1 and 3.

“Pembrolizumab 790 mg s.c.q6w administration was associated with relatively higher cycle 1 C trough and steadystate AUC 0-6 weeks , and relatively lower C max in both cycles 1 and 3 (Table 2).”

May combine two claims.

The observed incidence of treatment-emergent anti-drug antibodies was 1.4% (n=3) in the pembrolizumab s.c. arm and 0.9% (n=1) in the pembrolizumab i.v. arm.

“The observed incidence of treatment-emergent ADAs among assessable participants was 1.4% (n ¼ 3) in the pembrolizumab s.c.arm and 0.9% (n ¼ 1) in the pembrolizumab i.v.arm”

May combine two claims.

The median DOR was 9.1 months (range 6.9 months-not reached) in the pembrolizumab s.c. arm and 8.0 months (range 7.4 months-not reached) in the pembrolizumab i.v. arm.

“The median DOR was 9.1 months (range 6.9 months-not reached) in the pembrolizumab s.c.arm and 8.0 months (range 7.4 months-not reached) in the pembrolizumab i.v.arm”

May combine two claims.

The ORR was 45.4% (95% CI 39.1% to 51.8%) in the pembrolizumab s.c. arm and 42.1% (95% CI 33.3% to 51.2%) in the pembrolizumab i.v. arm (ORR ratio 1.08, 95% CI 0.85-1.37).

“The ORR was 45.4% (95% CI 39.1% to 51.8%) in the pembrolizumab s.c.arm and 42.1% (95% CI 33.3% to 51.2%) in the pembrolizumab i.v.arm (ORR ratio 1.08, 95% CI 0.85-1.37)”

May combine two claims.

Local injection-site adverse events with subcutaneous pembrolizumab administration were infrequent, mild, and nonserious.

“Local injection-site AEs with pembrolizumab s.c.administration were infrequent, mild, and nonserious.”

• Also stated in: § Annals of Oncology · plain

  “local injection-site AEs were infrequent, mild, and nonserious.”

May combine two claims.

All injection-site AEs were mild (grade 1) and nonserious.

“All injectionsite AEs were mild (grade 1) and nonserious.”

May combine two claims.

As of data cut-off, the median OS has not been reached in either treatment arm (HR 0.81, 95% CI 0.53-1.22).

“As of data cut-off, the median OS has not been reached in either treatment arm (HR 0.81, 95% CI 0.53-1.22).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The median time to onset of the first injection-site AEs from the most recent dose administration was 2.0 days (range 1-2 days).

“The median time to onset of the first injection-site AEs from the most recent dose administration was 2.0 days (range 1-2 days).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The median injection time per administration of pembrolizumab s.c. was 2.0 min (range 1-12 min).

“The median injection time per administration of pembrolizumab s.c. was 2.0 min (range 1-12 min).”

May combine two claims.

Overall exposure and trough concentration of subcutaneous pembrolizumab were noninferior to those of intravenous pembrolizumab.

“In summary, the 3475A-D77 study showed that overall exposure and trough concentration of pembrolizumab s.c. were noninferior to those of pembrolizumab i.v.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Lung cancer remains the most common malignancy worldwide.

“Treatment-naive mNSCLC was chosen as the indication to evaluate in this pharmacokinetic noninferiority study because lung cancer remains the most common malignancy worldwide.25”

• cites [25] Bray, 2024, Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J ClinNot checked yet

  Not checked in the free run.

May combine two claims.

Subcutaneous administration of therapeutic agents has advantages over intravenous administration, including higher patient satisfaction, lower emotional burden, and greater patient and provider preference.

“Subcutaneous (s.c.) administration of therapeutic agents has been shown to have advantages over intravenous (i.v.) administration, including higher patient satisfaction, lower emotional burden (e.g. less anxiety and stress), and greater patient and provider preference.[1][2][3][4]”

• cites [1][2][3][4]Not checked yet

  Not checked in the free run.

May combine two claims.

Both the IMscin001 and CheckMate 67T studies met their co-primary pharmacokinetic endpoints and showed comparable efficacy and safety between the s.c. and i.v. arms.

“Both studies met their co-primary pharmacokinetic endpoints and showed comparable efficacy and safety between the s.c. and i.v.arms.”

• cites [19] Albiges, 2025, Subcutaneous versus intravenous nivolumab for renal cell carcinoma, Ann Oncol sourceNot checked yet

  Not checked in the free run.

• cites [20] Burotto, 2023, Ann Oncol sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Consistent with the noninferiority of pharmacokinetic exposures of pembrolizumab s.c. and i.v., efficacy was similar between treatment arms.

“Consistent with the noninferiority of pharmacokinetic exposures of pembrolizumab s.c. and i.v., efficacy was similar between treatment arms.”

May combine two claims.

As of this analysis, the median duration of follow-up in the study is shorter than those of the KEYNOTE-189 and KEYNOTE-407 studies, and therefore the OS data are considered immature.

“As of this analysis, the median duration of follow-up in the study is shorter than those of the KEYNOTE-189 and KEYNOTE-407 studies.Therefore, the OS data are considered immature.”

Classified as probably not a substantial claim.

The noninferiority margin for the AUC 0-6 weeks and C trough geometric mean ratios of pembrolizumab s.c. versus i.v. was prespecified as 0.8.

“The noninferiority margin for the AUC 0-6 weeks and C trough was prespecified as 0.8.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Randomization was stratified by Eastern Cooperative Oncology Group performance status, histology, programmed death-ligand 1 tumor proportion score, and geographic region.

“Randomization was stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1), histology (squamous versus nonsquamous), programmed death-ligand 1 (PD-L1) tumor proportion score [<50% versus !50% as assessed centrally as per PD-L1 IHC 22C3 pharmDx (Agilent Technologies, Carpinteria, CA)], and geographic region (east Asia versus North America/western Europe/Australia/New”

Probably not a substantial claim: may not pass S3 (load-bearing).

All participants provided written informed consent.

“All participants provided written informed consent.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The trial was conducted in compliance with global standards, local and/or national regulations, International Council for Harmonisation Good Clinical Practice guidelines, and the Declaration of Helsinki.

“This trial was conducted in compliance with global standards, local and/or national regulations of each study site, and International Council for Harmonisation Good Clinical Practice guidelines, and in accordance with the ethical principles that have their origin in the Declaration of Helsinki.”

May combine two claims.

In both the IMscin001 and CheckMate 67T studies, immunogenicity was more pronounced with the s.c. drug than with the i.v. drug (IMscin001: 19.5% versus 13.9%; CheckMate 67T: 24.0% versus 6.9%), although neither study observed a meaningful clinical effect of ADA positivity.

“Notably, in both studies, immunogenicity was more pronounced with the s.c.drug than with the i.v.drug (IMscin001: 19.5% versus 13.9%; CheckMate 67T: 24.0% versus 6.9%), although neither study observed a meaningful clinical effect of ADA positivity.”

• cites [19] Albiges, 2025, Subcutaneous versus intravenous nivolumab for renal cell carcinoma, Ann Oncol sourceNot checked yet

  Not checked in the free run.

• cites [20] Burotto, 2023, Ann Oncol sourceNot checked yet

  Not checked in the free run.

May combine two claims.

As expected, pembrolizumab exposures at steady state were higher with pembrolizumab s.c. versus i.v., given that the amount of pembrolizumab per s.c. administration was selected to ensure that the exposure range for efficacy is maintained.

“As expected, pembrolizumab exposures at steady state were higher with pembrolizumab s.c.versus i.v., given that the amount of pembrolizumab per s.c.administration was selected to ensure that the exposure range for efficacy is maintained.”

Probably not a substantial claim: may not pass S3 (load-bearing).

All 377 randomized participants received treatment.

“All 377 randomized participants received treatment.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Efficacy was assessed in the intention-to-treat population.

“Efficacy was assessed in the intention-to treat population.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A time and motion study suggested that subcutaneous pembrolizumab can improve administration workflow by reducing active time for providers and chair time for patients.

“A time and motion study suggested that pembrolizumab s.c.can improve administration workflow by reducing active time for providers and chair time for patients.24”

• cites [24] De Cock E, Oskar S, Lourdudoss C, et al. A multi-country time & motion study of subcutaneous vs intravenous pembrolizumab plus chemotherapy in metastatic non-small cell lung cancer. Poster presented at the European Lung Cancer Congress 2025. 2025; Paris, France (poster number is 33P). sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Safety was assessed in all randomized participants who received at least one dose of study treatment.

“Safety was assessed in all randomized participants who received at least one dose of study treatment.”

May combine two claims.

Our study used a noninferiority design to evaluate the pharmacokinetics of pembrolizumab s.c. plus chemotherapy versus pembrolizumab i.v. plus chemotherapy, an approach that conforms to industry guidance and was employed to bridge the use of s.c. versus i.v. routes of administration for other cancer immunotherapies.

“Our study used a noninferiority design to evaluate the pharmacokinetics of pembrolizumab s.c.plus chemotherapy versus pembrolizumab i.v.plus chemotherapy, an approach that conforms to industry guidance and was employed to bridge the use of s.c.versus i.v.routes of administration for other cancer immunotherapies.[17][18][19][20]”

• cites [17][18][19][20]Not checked yet

  Not checked in the free run.

• AssumptionRests on an assumption: Pembrolizumab administered by intravenous infusion is approved globally for the treatment of multiple tumor types, including non-small-cell lung cancer.
• AssumptionRests on an assumption: Berahyaluronidase alfa acts as a permeation enhancer that temporarily degrades hyaluronan in the extracellular matrix surrounding the injection area, increasing dispersion and enabling subcutaneous administration of both every 3 weeks and every 6 weeks dosing regimens of pembrolizumab.

May combine two claims.

The graphical approach of Maurer et al. was used to control the overall type I error between the primary endpoints at a one-sided alpha level of 0.05, with 0.02 initially allocated to cycle 1 AUC 0-6 weeks and 0.03 to cycle 3 C trough.

“The graphical approach of Maurer et al. 14 was used to control the overall type I error between the primary endpoints at a one-sided a level of 0.05, with 0.02 initially allocated to cycle 1 AUC 0-6 weeks , and 0.03 to cycle 3 C trough .”

• cites Maurer et al. 14Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The subcutaneous pembrolizumab every-6-weeks regimen may allow for increased flexibility, especially for patients who would receive pembrolizumab in the early-stage setting, or in combination with chemotherapies or other agents of varying dosing schedules.

“the pembrolizumab s.c.q6w regimen may allow for increased flexibility, especially for patients who would receive pembrolizumab in the earlystage setting, or in combination with chemotherapies or other agents of varying dosing schedules.”

May combine two claims.

Establishing the pharmacokinetic noninferiority of subcutaneous pembrolizumab to intravenous pembrolizumab, both given with chemotherapy, as well as comparable efficacy and safety in non-small-cell lung cancer, may allow bridging to other approved pembrolizumab indications.

“Establishing the pharmacokinetic noninferiority of pembrolizumab s.c. to i.v., both given with chemotherapy, as well as comparable efficacy and safety in NSCLC, may allow bridging to other approved pembrolizumab indications.”

May combine two claims.

Subcutaneous pembrolizumab has the potential to improve the patient experience and reduce time demands in the clinic, which may streamline treatment center workflows and reduce health care resource utilization.

“with the potential to improve the patient experience and reduce time demands in the clinic, which may streamline treatment center workflows and reduce health care resource utilization.”