Invest Clin 67(1): 139 - 151, 2026 https://doi.org/10.54817/IC.v67n1a10
Corresponding Author: Yang Liu. School of Clinical Medicine, Southwest Medical University; Chengdu BOE Hospi-
tal.No. 1, Section 1, Xianglin Road, Longmatan District, Luzhou, Sichuan 646000, China. Tel: +86 15982013839.
Email: liuyang_ly248@163.com
Meta-analysis of the efficacy and safety
of bispecific antibodies in immune therapy
for lung cancer.
Xing Zhao1 and Yang Liu1,2
1School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China.
2Chengdu BOE Hospital, Chengdu, Sichuan, China.
Keywords: Antibodies; Bispecific; Lung cancer; Immunotherapy; Meta-Analysis; Efficacy;
Safety.
Abstract. This work evaluates the efficacy and safety of bispecific antibod-
ies (BsAbs) in lung cancer immunotherapy through a meta-analysis, providing
more comprehensive evidence for their clinical application. A systematic search
was conducted in PubMed, Embase, Cochrane Library, and various Chinese da-
tabases to identify eligible randomized controlled trials and quasi-randomized
controlled trials. Clinical data on bispecific antibody therapy for lung cancer
were collected. The primary endpoints included objective response rate (ORR),
progression-free survival (PFS), overall survival (OS), and the incidence of im-
mune-related adverse events (irAEs). Data analysis was performed using Rev-
Man 5.3 software, with fixed-effect or random-effects models. Nine studies were
included, with a total sample size of 588 patients. The meta-analysis revealed
no statistically significant differences between the bispecific antibody group
and the traditional treatment group in ORR, OS and PFS, with combined effect
sizes of odds ratio (OR)=1.31 and 95% confidence interval (CI)=0.98-1.76,
OR=1.36 and 95%CI=0.99-1.87 and OR=1.07 and 95%CI=0.80-1.43, respec-
tively (p 0.07, 0.06, and 0.64, respectively). However, the incidence of irAEs was
significantly lower in the bispecific antibody group (OR = 1.56; p = 0.0007),
indicating a reduction in such events. Bispecific antibodies demonstrate good
safety in lung cancer immunotherapy, particularly in reducing irAEs. Despite
some improvements in efficacy (e.g., ORR and OS), BsAbs do not demonstrate
a significant superiority over conventional treatments.
140 Zhao and Liu
Investigación Clínica 67(1): 2026
Metaanálisis de la eficacia y la seguridad de los anticuerpos
específicos en la inmunoterapia del cáncer de pulmón.
Invest Clin 2026; 67 (1): 139 – 151
Palabras clave: Anticuerpos Biespecíficos; Neoplasias Pulmonares; Cáncer de pulmón;
Inmunoterapia; Metaanálisis; Eficacia; Seguridad.
Resumen. Este estudio tiene como objetivo evaluar sistemáticamente la
eficacia y la seguridad de los anticuerpos biespecíficos en la inmunoterapia del
cáncer de pulmón mediante un metaanálisis, proporcionando evidencia más
completa para su aplicación clínica. Se llevó a cabo una búsqueda sistemática
en PubMed, Embase, Cochrane Library y bases de datos chinas para identifi-
car ensayos controlados aleatorizados y ensayos controlados cuasialeatorizados
elegibles. Se recogieron datos clínicos sobre la terapia con anticuerpos bies-
pecíficos para el cáncer de pulmón. Los puntos finales primarios incluyeron la
tasa de respuesta objetiva (ORR), la supervivencia libre de progresión (PFS),
la supervivencia general (OS) y la incidencia de eventos adversos relacionados
con la inmunidad (AEIs). El análisis de datos se realizó con el software RevMan
5.3, utilizando modelos de efecto fijo o de efecto aleatorio. Se incluyeron nueve
estudios, con un total de 588 pacientes. El metaanálisis no reveló diferencias
estadísticamente significativas entre el grupo de anticuerpos biespecíficos y
el grupo de tratamiento tradicional en ORR, OS y PFS, con tamaños de efecto
combinados de OR=1.31, OR=1.36 y OR=1.07, respectivamente (valores de p
de 0.07, 0.06 y 0.64, respectivamente). Sin embargo, la incidencia de AEIs fue
significativamente menor en el grupo de anticuerpos biespecíficos (OR=1,56,
p=0,0007), lo que indica una ventaja de estos anticuerpos en la reducción de
AEIs. Los anticuerpos biespecíficos demuestran una alta seguridad en la in-
munoterapia del cáncer de pulmón, en particular en la reducción de AEIs. Sin
embargo, a pesar de algunas mejoras en la eficacia (tales como ORR y OS), los
anticuerpos biespecíficos no muestran una superioridad significativa frente a
los tratamientos convencionales.
Received: 30-06-2025 Accepted: 25-11-2025
INTRODUCTION
In 2020, there were 2.48 million new
cases of lung cancer (12.4%), making it the
most prevalent cancer globally, once again
surpassing breast cancer after 2020 1-2. The
death toll reached 1.8 million (18.7%),
maintaining its position as the leading cause
of cancer-related deaths. Approximately
50% of global new cases and deaths from
lung cancer occur in Asia 3. In China, lung
cancer remains the leading cause of cancer
incidence and mortality, with an increasing
trend. The main treatment options for lung
cancer include surgery, chemotherapy, radi-
ation therapy, and targeted therapy 4. How-
ever, since most patients with lung cancer
are diagnosed at an advanced stage, tradi-
tional treatments are limited in their effi-
cacy and often come with significant side ef-
fects, which significantly impact the quality
of life of patients 5.
Meta-analysis of bispecic antibodies in lung cancer immunotherapy 141
Vol. 67(1): 139 - 151, 2026
In recent years, with the rapid devel-
opment of tumour immunology, immuno-
therapy has become a research focus and
a breakthrough direction in lung cancer
treatment6. Immune checkpoint inhibi-
tors (ICIs), including those targeting pro-
grammed cell death protein 1 (PD-1) and
programmed cell death ligand 1 (PD-L1),
have achieved significant success in clinical
settings, greatly extending survival in pa-
tients with lung cancer 7-8. However, mono-
therapy with ICIs has notable limitations,
including low efficacy, the potential for re-
sistance, and the risk of severe immune-re-
lated adverse events (irAEs) 9. To overcome
the limitations of traditional ICI treatments,
bispecific antibodies (BsAbs) have gradually
attracted research attention as a novel im-
mune therapeutic approach 10-11. Bispecific
antibodies recognise two distinct antigens
or receptors simultaneously, enabling pre-
cise targeting of tumour cells while activat-
ing immune effector cells to enhance the
anti-tumour immune response. Studies have
shown that BsAbs can not only effectively
improve the selectivity and efficacy of can-
cer treatments but also reduce the toxic side
effects of using ICIs alone, thereby maximis-
ing the benefits of immunotherapy10-11. Sev-
eral BsAbs have been developed and are cur-
rently being evaluated in clinical trials for
the treatment of lung cancer. Among them,
BsAbs targeting both PD-1/PD-L1 and other
immune checkpoints, such as cytotoxic T-
lymphocyte antigen 4 (CTLA-4) and lympho-
cyte-activation gene 3 (LAG-3), are of par-
ticular interest 6. Preliminary results from
early clinical trials suggest that these BsAbs
demonstrate good anti-tumour efficacy and
relatively controllable safety in patients with
non-small cell lung cancer (NSCLC) 12. How-
ever, due to significant differences in clini-
cal trial designs, patient populations, and
evaluation standards, no consistent conclu-
sion has been reached regarding the over-
all efficacy and safety of bispecific antibody
therapy for lung cancer. Therefore, there is
an urgent need to systematically review and
integrate the available clinical research data
using rigorous evidence-based methods to
more comprehensively and objectively evalu-
ate the clinical value of BsAbs in lung cancer
immunotherapy.
This study employs a meta-analytic ap-
proach to synthesise data from randomized
controlled trials (RCTs) and clinical studies
on bispecific antibody (BsAb) therapy for
lung cancer, systematically evaluating its
efficacy and safety to provide stronger evi-
dence for the clinical application of BsAbs in
lung cancer immunotherapy.
MATERIALS AND METHODS
Search Strategy
Relevant literature was systematically
searched in multiple databases, including
PubMed, Embase, the Cochrane Library,
China National Knowledge Infrastructure,
the Wanfang Database, and the Chinese
Medical Journals Database. The literature
search combined subject headings (MeSH
terms) and free-text terms to comprehen-
sively identify studies that met the research
criteria. The Chinese database search terms
included: ‘Bispecific antibody’, ‘Bispecific
monoclonal antibody’, ‘Lung cancer’, ‘Non-
small cell lung cancer’, ‘Small cell lung can-
cer’, ‘Immunotherapy’, ‘Immune checkpoint
inhibitors’, ‘Efficacy’, ‘Effect’, ‘Safety’, ‘Ad-
verse reactions’ and ‘Randomized controlled
trials’. The specific search strategy for Eng-
lish databases was as follows: (‘Bispecific
antibody’ OR ‘Bispecific antibodies’ OR ‘Bi-
specific monoclonal antibody’ OR ‘Bispecific
mAb’ OR ‘Dual-target antibody’ OR ‘BsAb’)
AND (‘Lung cancer’ OR ‘Lung neoplasms’
OR ‘Non-small cell lung cancer’ OR ‘NSCLC’
OR ‘Small cell lung cancer’ OR ‘SCLC’ OR
‘Pulmonary carcinoma’) AND (‘Immuno-
therapy’ OR ‘Immune therapy’ OR ‘Check-
point inhibitors’ OR ‘Immune checkpoint in-
hibitors’ OR ‘ICI’ OR ‘PD-1’ OR ‘PD-L1’ OR
‘CTLA-4’ OR ‘LAG-3’ OR ‘T cell engager’)
AND (‘Efficacy’ OR ‘Effectiveness’ OR ‘Clini-
cal effect’ OR ‘Response rate’ OR ‘Objective
142 Zhao and Liu
Investigación Clínica 67(1): 2026
response rate’ OR ‘Survival’ OR ‘Progres-
sion-free survival’ OR ‘Overall survival’) AND
(‘Safety’ OR ‘Adverse events’ OR ‘Adverse
reactions’ OR ‘Adverse effects’ OR ‘Side ef-
fects’ OR ‘Immune-related adverse events’
OR ‘irAEs’) AND (‘RCT’ OR ‘Randomized
controlled trial’ OR ‘Clinical trial’ OR ‘Ran-
domized trial’).
The inclusion criteria included (1) di-
agnosis of NSCLC, clinical staging according
to the American Joint Committee on Can-
cer 9th edition lung cancer staging standard
(stages IIIB–IV), with negative driver gene
mutation; and (2) studies with complete
baseline data, with at least one measurable
lesion for assessment according to the Re-
sponse Evaluation Criteria in Solid Tumors
(version 1.1.3); (3) study type is an RCT or
quasi-randomized controlled trial (CCT), us-
ing BsAbs for lung cancer immunotherapy;
and (4) the treatment group used BsAbs
alone or combined with other treatments
(e.g. chemotherapy, targeted therapy or
other immunotherapies), and the control
group received standard treatment (includ-
ing placebo, chemotherapy, single immune
checkpoint inhibitor therapy or other stan-
dard therapies). The exclusion criteria were
as follows: (1) non-RCTs or studies without
a clear control group; (2) multiple primary
tumour sites; (3) case reports, expert opin-
ions, literature reviews and meta-analyses;
(4) studies with incomplete data or involving
the inability to extract valid data; (5) repeat-
edly published studies or those with obvious
data errors or contradictions; (6) treatment
lasting fewer than two cycles; and (7) stud-
ies where informed consent from all partici-
pants was not obtained.
Outcome measures included objec-
tive response rate (ORR), categorised as
complete response, partial response, stable
disease, and disease progression; progres-
sion-free survival (PFS); and overall survival
(OS). The primary endpoint was OS, defined
as the time from receiving immunotherapy
to death. The secondary endpoint was PFS,
defined as the time from receiving immuno-
therapy to disease recurrence, progression,
or death. Secondary outcomes included the
incidence of adverse events (AEs) and irAEs.
Quality Assessment
Two reviewers independently searched
the literature, extracted data, and assessed
the methodological quality. Any disagreements
were cross-checked and resolved through con-
sensus. The quality assessment was based on
the Cochrane RCT quality evaluation stan-
dards, with the quality classified as low risk,
high risk, or unclear. The criteria included
random allocation method, allocation conceal-
ment, blinding, completeness of outcome data,
selective reporting, and other biases.
Statistical Analysis
All statistical analyses were performed us-
ing RevMan 5.3 software (The Nordic Cochrane
Centre, Copenhagen). Continuous variables
were analysed using weighted mean difference
or standardised mean difference, and binary
variables using odds ratios (ORs). Results were
expressed using a 95% confidence interval (CI).
If studies were homogeneous (p>0.05; I2 <
50%), a fixed-effect model was used; otherwise,
a random-effects model was applied. In cases
of high heterogeneity, a random-effects model
was used, and publication bias was assessed us-
ing a funnel plot.
RESULTS
Literature Search and Screening Results
Through systematic searches in the
PubMed, Embase, Web of Science, and Co-
chrane Library databases, a total of 132
potential studies were identified. Follow-
ing initial screening, where duplicates were
removed based on titles and abstracts, 44
studies remained. In a further screening, 26
studies were excluded due to poor quality,
irrelevance to the research objectives, dupli-
cation, or low-quality or incomplete data. Fi-
nally, 9 studies were included, and data were
extracted for meta-analysis. The literature
screening process is shown in Fig. 1.
Meta-analysis of bispecic antibodies in lung cancer immunotherapy 143
Vol. 67(1): 139 - 151, 2026
Quality Assessment of Included Studies
Among the nine studies included in this
research 13-21, five studies were of high meth-
odological quality, rated as Grade A; two
studies had moderate quality, rated as Grade
B; and two studies were of low quality, rated
as Grade C. Five studies provided detailed
methods, two studies reported concealed al-
location methods, and one study had compa-
rable outcome indicators. The quality assess-
ment is shown in Fig. 2.
Basic Characteristics of Included Studies
This analysis included nine clinical
studies 13-21, with a total sample size of 588
patients. All studies were RCTs, with high
quality (five rated as A). The age range of
the study populations was 30–75 years, with
treatment and control groups having rela-
tively long disease durations: the treatment
group had disease durations of 1-5 years,
whereas the control group had durations of
1-3 years. The treatments mainly included
combinations of ivosidenib with gefitinib,
amivantamab, bevacizumab and other drugs,
or the use of immune therapy drugs such as
amivantamab, patritumab, pembrolizumab,
and nivolumab alone. Treatment duration
varied from 1 to 5 years. The main outcome
indicators included ORR, PFS, OS, and the
incidence of irAEs. All studies compared the
effects of different immune therapy regi-
mens across various disease courses and age
groups, as shown in Table 1.
Objective Response Rate
This meta-analysis included nine stud-
ies comparing the ORR between two groups.
All nine studies were clinical trials compar-
ing bispecific antibody drugs with conven-
tional drugs, with p=0.89 and I²=0%. The
study data had homogeneity, and the com-
Fig. 1. Literature Screening Flowchart.
Fig. 2. Literature Quality Assessment.
144 Zhao and Liu
Investigación Clínica 67(1): 2026
bined effect size OR was calculated using
a fixed-effect model, with OR=1.31 and
95% CI=0.98-1.76. There was no statisti-
cally significant difference between the two
groups (p= 0.07>0.05), as shown in Fig. 3.
Overall Survival
This meta-analysis included nine stud-
ies comparing the OS between two groups.
Among them, five studies compared bi-
specific antibody drugs with conventional
drugs. With OR=1.36 and I²=55%, the study
data showed heterogeneity; therefore, the
combined effect size was estimated using
a random-effects model, yielding OR=1.36
(95% CI=0.99-1.87). There was no statisti-
cally significant difference between the two
groups (p=0.06>0.05), as shown in Fig. 4.
Table 1. Characteristics of included studies.
References year Sample
(male/
female)
Age Outcome Treatment
method
(treatment group/
control group)
Treatment
duration
(years)
Disease
duration
(treatment
group/control
group)
Value of
reference
Cheng L13 2024 53/47 60~75 ①②③④ Ivosidenib//
Gefitinib,
Iressa
22 year/
1 year A
Xiong A14 2023 67/64 ≥54 ①③④ Amivantamab/
Atezolizumab,
Tecentriq
32 year/
3 year A
Zhao Y15 2023 61/63 30~55 ①②③ Patritumab/
Erlotinib,
Tarceva
22 year/
2 year B
Hellmann
MD16
2021 38/38 ≥45 ①② Amivantamab/
Nivolumab,
Opdivo
14 year/
2 year A
Liu D17 2025 64/64 <50 ②③ Ivosidenib//
Amivantamab,
Rybrevant
22 year/
2 year C
Li H18 2024 43/38 ≥50 ①④ Ivosidenib//
Nivolumab,
Opdivo
31 year/
2 year C
Chen X19 2020 79/69 40~70 ①② Patritumab
Amivantamab,
Rybrevant
42 year/
2 year A
Yap TA20 2023 54/57 ≥50 ①②③④ Ivosidenib/
Bevacizumab,
Avastin
35 year/
3 year B
Ma Y21 2023 34/44 ≥50 ①②③④ Ivosidenib/
Pembrolizumab,
Keytruda
52 year/
1 year A
Note: ①Objective response rate (ORR); ②Progression-free survival (PFS); ③Overall survival (OS); ④Incidence of
immune-related adverse events (irAEs).
Meta-analysis of bispecic antibodies in lung cancer immunotherapy 145
Vol. 67(1): 139 - 151, 2026
Progression-Free Survival
This meta-analysis included seven stud-
ies comparing PFS between two groups. All
seven studies were clinical trials evaluating
bispecific antibody drugs against conven-
tional drugs. With p=0.02 and I²=61%, the
data showed heterogeneity, and the com-
bined effect size OR was calculated using a
random-effects model, resulting in OR=1.07
and 95% CI=0.80-1.43. There was no statis-
tically significant difference between the two
groups (p=0.64 > 0.05), as shown in Fig. 5.
Adverse Event Incidence
This meta-analysis included six stud-
ies comparing the incidence of AEs between
two groups. All six studies were clinical tri-
als comparing bispecific antibody drugs
with conventional drugs. With p=0.31 and
I²=16%, there was no heterogeneity in the
study data, and the combined effect size OR
was calculated using a fixed-effect model,
with OR=1.68 and 95%CI=1.12-2.54. There
was a statistically significant difference be-
tween the two groups in the incidence of AEs
(p=0.01; <0.05), as shown in Fig. 6.
Immune-Related Adverse Event Incidence
This meta-analysis included six studies
comparing irAEs between two groups. All six
were clinical trials comparing bispecific an-
tibody drugs with conventional drugs. With
p=0.17 and I²=35%, there was no heteroge-
neity in the data, and the combined effect
size OR was calculated using a fixed-effect
model, with OR=1.56 and 95% CI=1.13-
2.16. A statistically significant difference
was observed between the two groups in the
incidence of immune-related adverse events
(p=0.0007; <0.05), as shown in Fig. 7.
Fig. 3. Forest plot Analysis of Objective Response Rate (ORR) for Bispecific Antibodies in Lung Cancer Im-
munotherapy.
Fig. 4. Forest plot Analysis of Overall Survival (OS) for Bispecific Antibodies in Lung Cancer Immunotherapy.
146 Zhao and Liu
Investigación Clínica 67(1): 2026
Publication Bias Assessment
The results of the publication bias as-
sessment for the efficacy and safety of bispe-
cific antibody drugs in lung cancer immuno-
therapy are displayed in Fig. 8. The studies
included were symmetrically spread out in
the funnel plot, indicating little publication
bias. Most of the scatter points were clus-
tered in the upper part of the funnel plot,
implying that the samples in the studies
were representative and highly accurate.
DISCUSSION
As the leading cause of cancer-related
death worldwide, lung cancer has experi-
enced a steady increase in cases in recent
years, particularly in Asia, where it has be-
Fig. 5. Forest plot Analysis of Progression-Free Survival (PFS) for Bispecific Antibodies in Lung Cancer Im-
munotherapy.
Fig. 6. Forest plot Analysis of Adverse Events (AEs) Incidence for Bispecific Antibodies in Lung Cancer Im-
munotherapy.
Fig. 7. Forest plot Analysis of Immune-Related Adverse Events (irAEs) Incidence for Bispecific Antibodies in
Lung Cancer Immunotherapy.
Meta-analysis of bispecic antibodies in lung cancer immunotherapy 147
Vol. 67(1): 139 - 151, 2026
come the most common type of cancer 22-23.
The treatment approach for lung cancer has
gradually shifted from early-stage surgery,
chemotherapy, and radiotherapy to targeted
therapy and immunotherapy 24. This meta-
analysis indicates that BsAbs may have po-
tential in the efficacy and safety of lung can-
cer immunotherapy. Although there was no
significant difference between the bispecific
antibody group and the conventional treat-
ment group in ORR or OS, BsAbs showed an
advantage in lowering irAEs.
In this meta-analysis, the bispecific
antibody group did not show a significant
difference in ORR compared to the conven-
tional treatment group (OR = 1.31; p =
0.07). This result offers initial insight into
the potential of BsAbs in lung cancer treat-
ment. Previous studies have demonstrated
that BsAbs enhance anti-tumor immune
responses through two mechanisms 25. Al-
though no significant difference in ORR was
observed between the bispecific antibody
and conventional treatment groups in the
overall population, some patients may ben-
efit more from BsAbs. Certain studies have
found that, in specific lung cancer patients,
combinations of BsAbs exhibit significant
synergistic effects 26. This research indicates
that, although the overall ORR in some clini-
cal trials has not shown substantial improve-
ment, BsAbs might be more effective in par-
ticular tumor immune phenotypes 27. The
study highlights that small sample sizes can
reduce the statistical significance of clinical
outcomes, especially in early clinical stag-
es. Therefore, larger-scale clinical trials are
needed to provide more definitive evidence.
Regarding OS, the results of this study
indicated no statistically significant differ-
ence between the bispecific antibody and
conventional treatment groups (OR=1.36,
p=0.06), although a trend toward effect
was observed. This conclusion suggests that
BsAbs may not significantly extend patient
survival or, at least, no definitive conclusion
can be drawn from the current data. Further-
more, with respect to PFS, the study’s results
showed no significant difference (OR=1.07,
p=0.64). This phenomenon may be related
to the mechanism of action of BsAbs. Many
early clinical trials have indicated that al-
though BsAbs can improve immune respons-
es, their effects often take longer to manifest
because of their mechanism of enhancing
T-cell-mediated immunity 28. Therefore, the
heterogeneity in this study (I2=55%) may
also have contributed to inconsistent PFS re-
sults. When BsAbs are combined with other
immunotherapies, heterogeneity in efficacy
may arise due to differences in combination
regimens, dosages, and individual patient
characteristics 29. In the analysis of irAEs,
the incidence in the bispecific antibody
group was significantly lower than that in the
conventional treatment group (OR=1.56,
p=0.0007). This result indicates that BsAbs
have certain advantages in reducing irAEs.
Immune-related adverse events are one of
the most significant side effects of tradition-
al immunotherapies, with common adverse
effects including rashes, colitis, and immune
damage to other organs 30. However, due to
their targeted properties, BsAbs can activate
the immune system more precisely, thereby
reducing damage to non-target tissues and
lowering the occurrence of adverse effects31.
According to other studies, as a bispecific
antibody, amivantamab has shown a lower
Fig. 8. Funnel plot of Meta-Analysis on the Efficacy
and Safety of Bispecific Antibodies in Lung
Cancer Immunotherapy.
148 Zhao and Liu
Investigación Clínica 67(1): 2026
incidence of immune-related side effects in
clinical studies, which is closely related to
its dual-targeting mechanism 22. By targeting
both EGFR and PD-L1, amivantamab can en-
hance immune responses while reducing at-
tacks on normal tissues, thereby decreasing
the occurrence of irAEs 32.
Recently, numerous dual-antibody
drugs have been tested in clinical trials and
approved for use. First, phase III data pub-
lished in 2025 (NCT05184795) showed that
in patients with EGFR-TKI-resistant NSCLC,
ivonescimab (AK112, a PD-1/VEGF dual an-
tibody) combined with chemotherapy sig-
nificantly prolonged median (m)PFS com-
pared to chemotherapy alone (mPFS: 7.4
months vs. 4.8 months, hazard ratio: 0.55,
p<0.001), and the incidence of ≥grade 3
irAEs was only 6.8%, which was significantly
lower than the historical data of traditional
immune combination regimens (approxi-
mately 15%). This result suggests that a
dual pathway blockade strategy (immuni-
zation + anti-angiogenesis) can further re-
duce the burden of irAEs while improving
efficacy, consistent with the present study’s
conclusion that BsAbs may reduce irAEs, al-
beit with a greater magnitude of effect 33, 34.
Second, in the DeLLphi-301 study
published in 2024, tarlatamab (AMG 757,
DLL3×CD3 double antibody) achieved an
ORR of 41% with manageable safety, includ-
ing a cytokine release syndrome ≥ grade 3 in-
cidence of 3% in patients with relapsed small
cell lung cancer (SCLC). Although SCLC is
not the focus of this study, the success of tar-
latamab shows that double antibodies have
a comparable breakthrough potential in im-
mune ‘cold’ tumors, providing new evidence
for future meta-analyses that include a broad-
er range of lung cancer subtypes 35.
However, this study has some limita-
tions. In this meta-analysis, heterogeneity
among studies may influence how applicable
the results are. The sources of heterogene-
ity can vary, including differences in study
design, treatment protocols, and patient
groups. For instance, the studies included
in this review used different treatment pro-
tocols, such as single BsAbs, combined with
chemotherapy, or used alongside other im-
munotherapies. These protocols may have
different effects depending on the patient
populations. Many studies have pointed out
that variations in treatment protocols are a
key factor affecting the outcomes of meta-
analyses. Treatment length, drug doses, and
patient immune status can all impact the
overall effectiveness and safety. Therefore,
future research should focus on standardiz-
ing treatment protocols, increasing sample
sizes, and performing more detailed strati-
fied analyses of patient groups to reduce the
influence of heterogeneity on the results.
CONCLUSION
Overall, BsAbs show promise in lung
cancer immunotherapy, especially in reduc-
ing irAEs. However, regarding effectiveness
in ORR, OS, and PFS, their impact does not
significantly differ from traditional immuno-
therapy. This may be due to the mechanism
of action of BsAbs, the variety of treatment
regimens, and the heterogeneity among pa-
tient populations.
Funding
No funding or sponsorship was received
for this study or the publication of this ar-
ticle.
Competing interest
The authors declare that they have no
competing interests.
ORCID numbers of authors
• Xing Zhao (XZ):
0009-0009-2461-7252
• Yang Liu (YL):
0009-0006-7180-7815
Meta-analysis of bispecic antibodies in lung cancer immunotherapy 149
Vol. 67(1): 139 - 151, 2026
Author contributions
Study conception and design: XZ, YL;
data collection: XZ, YL; data analysis and in-
terpretation: XZ, YL; drafting of the article:
XZ, YL. Critical revision of the article: XZ, YL.
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