NCT02923349

A Phase 1/2, Open-Label, Dose-Escalation, Safety Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors

Completed Phase 1, PHASE2 Results posted Last updated 24 August 2025

What this trial tests

Phase 1, PHASE2 trial testing INCAGN01949 in Advanced Malignancies in 87 participants. Completed in 26 March 2019.

Timeline

31 October 2016

Primary endpoint
26 March 2019

26 March 2019

Quick facts

Lead sponsor	Incyte Biosciences International Sàrl
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	87
Start date	31 October 2016
Primary completion	26 March 2019
Estimated completion	26 March 2019
Sites	8 locations across Switzerland, United Kingdom, United States, Spain

Drugs / interventions tested

• INCAGN01949 — full drug profile →

Conditions studied

• Advanced Malignancies — all drugs for Advanced Malignancies →
• Metastatic Cancer — all drugs for Metastatic Cancer →

Sponsor

Incyte Biosciences International Sàrl — full company profile →

Who can join

18 and older, any sex, with Advanced Malignancies or Metastatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Observed Concentration (Cmax) of INCAGN01949 in Plasma Secondary · Pre-infusion for cycles 1,2,3,4,5,6 and 7, 10-minutes, 4 hrs, 24 hrs post-infusion, Day 8 for cycles 1 & 6

To evaluate the Cmax of INCAGN01949 in subjects with advanced or metastatic solid tumors.

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	1630	± 735
PART 1 Dose 2 (20 mg)	5820	± 324
PART 1 Dose 3 (70 mg)	22300	± 32800
PART 1 Dose 4 (200 mg)	39200	± 10300
PART 1 Dose 5 (350 mg)	84900	± 76700
PART 1 Dose 6 (700 mg)	207000	± 45500
PART 1 Dose 7 (1400 mg)	347000	± 130000

Area Under the Single-dose Concentration-time Curve (AUC0-t) of INCAGN01949 Secondary · Pre-infusion for cycles 1,2,3,4,5,6 and 7, 10-minutes, 4 hrs, 24 hrs post-infusion, Day 8 for cycles 1 & 6

To evaluate the AUC0-t of INCAGN01949 in subjects with advanced or metastatic solid tumors

cycle 1

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	185	± 81.7
PART 1 Dose 2 (20 mg)	904	± 197
PART 1 Dose 3 (70 mg)	2370	± 841
PART 1 Dose 4 (200 mg)	5400	± 1820
PART 1 Dose 5 (350 mg)	10000	± 5600
PART 1 Dose 6 (700 mg)	28300	± 7720
PART 1 Dose 7 (1400 mg)	61600	± 9130

cycle 6

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	427	± 9.21
PART 1 Dose 3 (70 mg)	5490	± 1560
PART 1 Dose 4 (200 mg)	10700	± 6560

Objective Response Rate Per RECIST and Modified RECIST Secondary · Baseline and every 8 weeks,up to 11 months

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 and mRECIST v1.1. by investigator determination.

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	0
PART 1 Dose 2 (20 mg)	0
PART 1 Dose 3 (70 mg)	0
PART 1 Dose 4 (200 mg)	0
PART 1 Dose 5 (350 mg)	0
PART 1 Dose 6 (700 mg)	1
PART 1 Dose 7 (1400 mg)	0

Duration of Response Per RECIST and Modified RECIST Secondary · Baseline and every 8 weeks, up to 11 months

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 and mRECIST v1.1. by investigator determination.

Group	Value	95% CI
PART 1 Dose 6 (700 mg)	192	192 – 192

Progression-free Survival Per RECIST and Modified RECIST Secondary · Baseline and every 8 weeks, up to 11 months

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 and mRECIST v1.1. by investigator determination.

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	57	55 – 59
PART 1 Dose 2 (20 mg)	47.5	29 – 112
PART 1 Dose 3 (70 mg)	54.0	23 – 216
PART 1 Dose 4 (200 mg)	56.0	26 – 281
PART 1 Dose 5 (350 mg)	52.0	1 – 166
PART 1 Dose 6 (700 mg)	125.0	21 – 298
PART 1 Dose 7 (1400 mg)	46.5	42 – 53

Duration of Disease Control Per RECIST and Modified RECIST Secondary · Baseline and every 8 weeks, up to 11 months

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 and mRECIST v1.1. by investigator determination.

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	0	0 – 0
PART 1 Dose 2 (20 mg)	57	57 – 57
PART 1 Dose 3 (70 mg)	64	1 – 160
PART 1 Dose 4 (200 mg)	57	1 – 225
PART 1 Dose 5 (350 mg)	NA	1 – 112
PART 1 Dose 6 (700 mg)	120	1 – 249

Number of Participants With Treatment-related Adverse Events Primary · From screening through 60 days after end of treatment, up to 11 months

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	4
PART 1 Dose 2 (20 mg)	4
PART 1 Dose 3 (70 mg)	21
PART 1 Dose 4 (200 mg)	17
PART 1 Dose 5 (350 mg)	22
PART 1 Dose 6 (700 mg)	11
PART 1 Dose 7 (1400 mg)	4

Time to Maximum Concentration of INCAGN01949 in Plasma Secondary · Pre-infusion for cycles 1,2,3,4,5,6 and 7, 10-minutes, 4 hrs, 24 hrs post-infusion, Day 8 for cycles 1 & 6

To evaluate the Tmax of INCAGN01949 in subjects with advanced or metastatic solid tumors.

cycle 1

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	0.64	0.6 – 4.4
PART 1 Dose 2 (20 mg)	2.53	0.55 – 4.5
PART 1 Dose 3 (70 mg)	4.3	0.50 – 25.2
PART 1 Dose 4 (200 mg)	0.63	0.5 – 4.5
PART 1 Dose 5 (350 mg)	0.6	0.0 – 194
PART 1 Dose 6 (700 mg)	0.7	0.53 – 4.2
PART 1 Dose 7 (1400 mg)	0.73	0.0 – 2.43

cycle 6

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	0.78	0.75 – 0.8
PART 1 Dose 3 (70 mg)	0.63	0.50 – 4.3
PART 1 Dose 4 (200 mg)	0.61	0.55 – 4.8

Summary of Trough Concentrations(Cmin) of INCAGN01949 Secondary · Pre-infusion for cycles 1,2,3,4,5,6 and 7, 10-minutes, 4 hrs, 24 hrs post-infusion, Day 8 for cycles 1 & 6

To evaluate the Cmin of INCAGN01949 in subjects with advanced or metastatic solid tumors. Cmin is the minimum observed concentration of INCAGN1949

cycle 2

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	303	± 202
PART 1 Dose 2 (20 mg)	1890	± 1570
PART 1 Dose 3 (70 mg)	3620	± 1550
PART 1 Dose 4 (200 mg)	8880	± 4510
PART 1 Dose 5 (350 mg)	17000	± 8040
PART 1 Dose 6 (700 mg)	41000	± 13000
PART 1 Dose 7 (1400 mg)	117000	± 19300

cycle 3

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	753	± 163
PART 1 Dose 2 (20 mg)	1520	± 225
PART 1 Dose 3 (70 mg)	5620	± 3280
PART 1 Dose 4 (200 mg)	14300	± 7740
PART 1 Dose 5 (350 mg)	29400	± 18400
PART 1 Dose 6 (700 mg)	77800	± 27900
PART 1 Dose 7 (1400 mg)	163000	± 32900

cycle 4

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	895	± 80.2
PART 1 Dose 2 (20 mg)	1780	± 318
PART 1 Dose 3 (70 mg)	5110	± 2850
PART 1 Dose 4 (200 mg)	17900	± 13200
PART 1 Dose 5 (350 mg)	42200	± 28500
PART 1 Dose 6 (700 mg)	84600	± 17700
PART 1 Dose 7 (1400 mg)	282000	± 165000

cycle 6

Group	Value	95% CI
PART 1 Dose 1 (7 mg)	785	± 39.6
PART 1 Dose 3 (70 mg)	9150	± 2420
PART 1 Dose 4 (200 mg)	19600	± 13100
PART 1 Dose 5 (350 mg)	43400	± 26500

cycle 7

Group	Value	95% CI
PART 1 Dose 3 (70 mg)	10200	± 2190
PART 1 Dose 4 (200 mg)	21600	± 10600

Adverse events — posted to ClinicalTrials.gov

Time frame: From screening through 60 days after end of treatment, up to 11 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PART 1 Dose 1 (7 mg)

Serious: 1/4 (25%)

Deaths: 1/4

PART 1 Dose 2 (20 mg)

Serious: 1/4 (25%)

Deaths: 0/4

PART 1 Dose 3 (70 mg)

Serious: 8/22 (36%)

Deaths: 2/22

PART 1 Dose 4 (200 mg)

Serious: 9/18 (50%)

Deaths: 4/18

PART 1 Dose 5 (350 mg)

Serious: 9/23 (39%)

Deaths: 2/23

PART 1 Dose 6 (700 mg)

Serious: 5/12 (42%)

Deaths: 3/12

PART 1 Dose 7 (1400 mg)

Serious: 1/4 (25%)

Deaths: 0/4

Serious adverse events (38 terms)

Reaction	System	PART 1 Dose 1 (7 mg)	PART 1 Dose 2 (20 mg)	PART 1 Dose 3 (70 mg)	PART 1 Dose 4 (200 mg)	PART 1 Dose 5 (350 mg)	PART 1 Dose 6 (700 mg)	PART 1 Dose 7 (1400 mg)
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—	—
Appendicitis	Infections and infestations	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—	—	—	—
Ataxia	Nervous system disorders	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Cauda equina syndrome	Nervous system disorders	—	—	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Embolism	Vascular disorders	—	—	—	—	—	—	—
General physical health deterioration	General disorders	—	—	—	—	—	—	—
Hydronephrosis	Renal and urinary disorders	—	—	—	—	—	—	—
Intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—
Jaundice	Hepatobiliary disorders	—	—	—	—	—	—	—
Jaundice cholestatic	Hepatobiliary disorders	—	—	—	—	—	—	—
Lower respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Lower respiratory tract infection bacterial	Infections and infestations	—	—	—	—	—	—	—

Other adverse events (118 terms — click to expand)

Reaction	System	PART 1 Dose 1 (7 mg)	PART 1 Dose 2 (20 mg)	PART 1 Dose 3 (70 mg)	PART 1 Dose 4 (200 mg)	PART 1 Dose 5 (350 mg)	PART 1 Dose 6 (700 mg)	PART 1 Dose 7 (1400 mg)
Fatigue	General disorders	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—
Amylase increased	Investigations	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Epigastric discomfort	Gastrointestinal disorders	—	—	—	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—	—	—	—
Hypoaesthesia	Nervous system disorders	—	—	—	—	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Night sweats	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Peripheral swelling	General disorders	—	—	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Seasonal allergy	Immune system disorders	—	—	—	—	—	—	—
Skin infection	Infections and infestations	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Malignant neoplasm progression, Abdominal pain, Small intestinal obstruction, Abdominal pain upper, Acute kidney injury, Appendicitis, Arthralgia, Ascites.

Data from ClinicalTrials.gov NCT02923349 adverse events section.

Sponsor's own description

The purpose of this study is to determine the safety and tolerability and assess preliminary efficacy of INCAGN01949 in subjects with advanced or metastatic solid tumors.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immunotherapy in colorectal cancer: rationale, challenges and potential.
   Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, et al · · 2019 · cited 1407× · PMID 30886395 · DOI 10.1038/s41575-019-0126-x
2. Next generation of immune checkpoint therapy in cancer: new developments and challenges.
   Marin-Acevedo JA, Dholaria B, Soyano AE, Knutson KL, et al · · 2018 · cited 582× · PMID 29544515 · DOI 10.1186/s13045-018-0582-8
3. Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends.
   Sun Q, Hong Z, Zhang C, Wang L, et al · · 2023 · cited 387× · PMID 37635168 · DOI 10.1038/s41392-023-01522-4
4. Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors.
   Melaiu O, Lucarini V, Cifaldi L, Fruci D. · · 2019 · cited 324× · PMID 32038612 · DOI 10.3389/fimmu.2019.03038
5. Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity.
   Fu Y, Lin Q, Zhang Z, Zhang L. · · 2020 · cited 200× · PMID 32140389 · DOI 10.1016/j.apsb.2019.08.010
6. Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy.
   Boyero L, Sánchez-Gastaldo A, Alonso M, Noguera-Uclés JF, et al · · 2020 · cited 78× · PMID 33322522 · DOI 10.3390/cancers12123729
7. First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors.
   Davis EJ, Martin-Liberal J, Kristeleit R, Cho DC, et al · · 2022 · cited 56× · PMID 36316061 · DOI 10.1136/jitc-2021-004235
8. Next generation immune-checkpoints for cancer therapy.
   Donini C, D'Ambrosio L, Grignani G, Aglietta M, et al · · 2018 · cited 50× · PMID 29951308 · DOI 10.21037/jtd.2018.02.79