NCT02994953 (COMBO) is a Phase 1 clinical trial of Avelumab in Advanced Solid Tumors, sponsored by EMD Serono Research & Development Institute, Inc..

Who is sponsoring NCT02994953?

NCT02994953 is sponsored by EMD Serono Research & Development Institute, Inc..

What drugs are being tested in NCT02994953?

Interventions in NCT02994953: Avelumab, M9241, Avelumab (Once weekly), M9241 (MTD), Avelumab (Expansion cohort).

What condition does NCT02994953 study?

NCT02994953 studies Advanced Solid Tumors.

Is NCT02994953 still recruiting?

NCT02994953 is currently terminated. Last updated 20 September 2024.

Are results published for NCT02994953?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2024-09-20 · How we verify

NCT02994953: COMBO

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

A Phase Ib Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) of Avelumab in Combination With M9241(NHS-IL12) (JAVELIN IL-12)

Terminated Phase 1 Results posted Last updated 20 September 2024

What this trial tests

Phase 1 trial testing Avelumab in Advanced Solid Tumors in 52 participants. Terminated before completion.

Timeline

31 January 2017

Primary endpoint
8 October 2020

8 October 2020

Quick facts

Lead sponsor	EMD Serono Research & Development Institute, Inc.
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	52
Start date	31 January 2017
Primary completion	8 October 2020
Estimated completion	8 October 2020
Sites	33 locations across France, Italy, Netherlands, Belgium, Hungary, United States, Spain

Drugs / interventions tested

Avelumab (avelumab) — full drug profile →
M9241 — full drug profile →
Avelumab (Once weekly) — full drug profile →
M9241 (MTD)
Avelumab (Expansion cohort) — full drug profile →

Conditions studied

Advanced Solid Tumors — all drugs for Advanced Solid Tumors →

Sponsor

EMD Serono Research & Development Institute, Inc. — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors. 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.

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 Primary · From first dose of study treatment up to 1311 days

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worse

Participants with TEAEs

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	9
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	7
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	7
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	6
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	7

Participants with Treatment-related-TEAEs

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	8
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	5
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	6
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	5
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	6

Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 Primary · Part B: From first dose of study treatment up to 443 days

Participants with TEAEs

Group	Value	95% CI
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	16

Participants with Treatment-Related AEs

Group	Value	95% CI
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	15

Part A: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity Based on Grade 3,4 and 5 According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) Primary · From first dose of study treatment up to 1311 days

AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grade 3,4 and 5 by severity were only reported.

Grade >=3

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	6
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	5
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	6
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	4
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	4

Grade >=4

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	2
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	2
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	2
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	2
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	1

Grade 5

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	0
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	1
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	0
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	1
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	1

Part B: Number of Participants With Treatment-Related Adverse Events (TRAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) Primary · First dose of study drug up to 443 days

AE was any untoward medical occurrence in a participants who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment. Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs and TRAEs by severity were reported.

Any Grade

Group	Value	95% CI
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	15

Grade >=3

Group	Value	95% CI
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	8

Grade >=4

Group	Value	95% CI
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	1

Grade 5

Group	Value	95% CI
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	0

Part A: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Primary · Time from first treatment to final assessment up to 3 weeks

A DLT is any Grade (\>=) 3 non-hematologic AE or any Grade (\>=) 4 hematologic AE according to the NCI-CTCAE v4.03, occurring during the DLT observation period that is related to either or both study drugs as determined by the Investigator or Sponsor at any dose and judged not to be related to the underlying disease or any previous or concomitant medication. The following are exceptions to the DLTs: Grade \>=3 thrombocytopenia with medically concerning bleeding; Any Grade 3 autoimmune thyroid-related toxicity that doesn't clinically resolve to \<= Grade 2 within 7 days of initiating therapy wi

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	0
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	0
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	1
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	0
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	0

Part B: Number of Participants With Confirmed Best Overall Response (BOR) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Primary · First dose of study drug up to 443 days

Confirmed BOR was defined as the best response of any of the confirmed complete response (CR), confirmed partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference).CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of di

Group	Value	95% CI
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	0
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	0
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	2
Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)	13

Part A: Area Under Serum Concentration Time Curve From Time Zero to the Time of the Last Observation (AUC0-t) of Avelumab Secondary · Predose (PrD),1,4,8 hours postdose (PD) on Day 1,22 of Cycle 1 & 2; PrD,1 hour PD on Day 8,15 of Cycle 1 & Day 8,15,22 of Cycle 2; PrD, 1 hour PD on Day 1 Cycle 3 & Day 1,15 of Cycle 4; PrD on Day 1 of Cycle 7,10,13,16,19,22,25, & 28 (Each cycle: 28 days)

Area under the serum concentration versus time curve from time zero to the last sampling time t at which concentration is at or above the lower limit of quantification (LLLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

Cycle 1 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	20700	± 38.1
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	26600	± 57.9
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	23600	± 16.6
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	17400	± 33.4
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	17900	± 39.7

Cycle 1 Day 15

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	22800	± 40.5
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	26100	± 42.5
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	28300	± 39.4
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	22000	± 19.2

Cycle 1 Day 22

Group	Value	95% CI
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	26300	± 31.0

Cycle 2 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	26400	± 17.2
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	27900	± 47.9
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	22700	± 23.2
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	22700	± 10.5
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	22100	± 42.7

Part A: Area Under Serum Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab Secondary · PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

Cycle 1 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	22300	± 41.5
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	30100	± 75.8
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	26500	± 21.5
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	18800	± 29.5
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	27000	± 65.0

Cycle 1 Day 15

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	26300	± 37.2
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	29800	± 35.7
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	27100	± 34.5
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	23000	± 26.0

Cycle 1 Day 22

Group	Value	95% CI
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	43400	± 56.1

Cycle 2 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	29800	± 18.4
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	33100	± 48.4
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	24300	± 30.6
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	24400	± 13.3
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	35100	± 40.3

Part A: Terminal Elimination Rate Constant (Lambdaz) of Avelumab Secondary · PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

Lambda(z) was determined from the terminal slope of the log-transformed serum concentration curve using linear regression method.

Cycle 1 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	0.00847	± 29.6
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	0.00729	± 48.5
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	0.00756	± 20.6
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	0.00790	± 14.4
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	0.00822	± 37.1

Cycle 1 Day 15

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	0.00780	± 31.6
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	0.00814	± 15.7
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	0.00780	± 31.4
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	0.00803	± 17.1

Cycle 1 Day 22

Group	Value	95% CI
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	0.00620	± 34.3

Cycle 2 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	0.00659	± 15.7
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	0.00714	± 39.8
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	0.00868	± 19.2
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	0.00830	± 16.4
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	0.00793	± 35.9

Part A: Maximum Observed Serum Concentration (Cmax) of Avelumab Secondary · PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.

Cycle 1 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	241	± 39.9
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	244	± 29.9
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	287	± 36.4
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	156	± 67.7
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	228	± 29.3

Cycle 1 Day 15

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	229	± 54.4
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	250	± 14.6
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	256	± 32.0
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	201	± 25.6

Cycle 1 Day 22

Group	Value	95% CI
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	269	± 44.0

Cycle 2 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	213	± 21.3
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	249	± 37.5
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	210	± 19.7
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	200	± 8.1
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	318	± 33.5

Part A: Minimum Observed Serum Concentration (Cmin) of Avelumab Secondary · PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

Cmin is minimum observed serum concentration obtained directly from the concentration versus time curve.

Cycle 1 Day 15

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	11.3	± 90.4
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	14.5	± 37.2
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	14.0	± 70.3
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	9.28	± 51.8

Cycle 1 Day 22

Group	Value	95% CI
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	74.1	± 62.0

Cycle 2 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	20.5	± 37.6
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	24.0	± 79.9
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	14.4	± 91.9
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	13.1	± 24.4
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	59.3	± 122.5

Part A: Time to Reach Maximum Observed Concentration (Tmax) of Avelumab Secondary · PrD, 1, 4, 8 hours PD on Day 1, 22 of cycle 1 & 2; PrD, 1 hour PD on Day 8, 15 of cycle 1 & Day 8, 15, 22 of cycle 2; PrD, 1 hour PD on Day 1 cycle 3 & Day 1, 15 of cycle 4; PrD on Day 1 of cycle 7, 10,13,16,19,22,25, & 28 (Each cycle: 28 days)

Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.

Cycle 1 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	4.00	1.00 – 25.08
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	1.05	1.00 – 9.00
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	3.90	1.00 – 4.25
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	2.58	1.00 – 44.78
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	4.00	1.00 – 22.20

Cycle 1 Day 15

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	5.04	1.00 – 48.42
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	1.13	1.00 – 25.72
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	4.00	1.22 – 49.00
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	4.09	1.03 – 29.18

Cycle 1 Day 22

Group	Value	95% CI
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	4.00	1.00 – 43.03

Cycle 2 Day 1

Group	Value	95% CI
Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg	1.58	1.13 – 25.00
Part A Cohort 2: M9241 8 mcg/kg + Avelumab 10 mg/kg	1.17	1.10 – 4.08
Part A Cohort 3: M9241 12 mcg/kg + Avelumab 10 mg/kg	23.07	3.98 – 25.00
Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg	2.00	1.00 – 25.35
Part A Cohort 5: M9241 16.8 mcg/kg + Avelumab 800 mg	4.00	1.12 – 9.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Part A: Baseline up to 1311 days Part B: Baseline up to 443 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A Cohort 1: M9241 4 mcg/kg + Avelumab 10 mg/kg (Experimental)

Serious: 4/9 (44%)

Deaths: 9/9

Part A Cohort 2: M9241 8 mcg/kg +Avelumab 10 mg/kg

Serious: 4/7 (57%)

Deaths: 5/7

Part A Cohort 3: M9241 12 mcg/kg +Avelumab 10 mg/kg

Serious: 3/7 (43%)

Deaths: 6/7

Part A Cohort 4: M9241 16.8 mcg/kg +Avelumab 10 mg/kg

Serious: 3/6 (50%)

Deaths: 5/6

Part A Cohort 5: M9241 16.8 mcg/kg +Avelumab 800 mg

Serious: 4/7 (57%)

Deaths: 7/7

Part B Cohort 1: UC Cohort Stage 1 Combination Therapy (Experimental)

Serious: 12/16 (75%)

Deaths: 12/16

Serious adverse events (41 terms)

Reaction	System	Part A Cohort 1: M9241 4 m…	Part A Cohort 2: M9241 8 m…	Part A Cohort 3: M9241 12 …	Part A Cohort 4: M9241 16.…	Part A Cohort 5: M9241 16.…	Part B Cohort 1: UC Cohort…
Disease progression	General disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Hyperthermia	General disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Autoimmune haemolytic anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Blood loss anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—	—	—	—
Large intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—
Retroperitoneal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Gallbladder obstruction	Hepatobiliary disorders	—	—	—	—	—	—
Immune-mediated hepatitis	Hepatobiliary disorders	—	—	—	—	—	—
Cytokine release syndrome	Immune system disorders	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Haemorrhage intracranial	Nervous system disorders	—	—	—	—	—	—
Confusional state	Psychiatric disorders	—	—	—	—	—	—
Cystitis noninfective	Renal and urinary disorders	—	—	—	—	—	—
Renal haemorrhage	Renal and urinary disorders	—	—	—	—	—	—

Other adverse events (179 terms — click to expand)

Reaction	System	Part A Cohort 1: M9241 4 m…	Part A Cohort 2: M9241 8 m…	Part A Cohort 3: M9241 12 …	Part A Cohort 4: M9241 16.…	Part A Cohort 5: M9241 16.…	Part B Cohort 1: UC Cohort…
Pyrexia	General disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Influenza like illness	General disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Hyperthermia	General disorders	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Cytokine release syndrome	Immune system disorders	—	—	—	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Haematuria	Renal and urinary disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Hypotension	Vascular disorders	—	—	—	—	—	—
Thrombocytosis	Blood and lymphatic system disorders	—	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—

Most-reported serious reactions: Disease progression, Pyrexia, Diarrhoea, Hyperthermia, Anaemia, Autoimmune haemolytic anaemia, Blood loss anaemia, Supraventricular tachycardia.

Data from ClinicalTrials.gov NCT02994953 adverse events section.

Sponsor's own description

The study consisted of 2 parts: Dose Escalation phase (Part A) and Expansion phase (Part B). The dose escalation phase evaluated the safety, tolerability, and PK of avelumab in combination with M9241 in subjects with locally advanced, unresectable, or metastatic solid tumors. Expansion phase assessed the safety and clinical activity of the combination regimen in selected tumor types. In Expansion phase subjects who had completed the combination treatment of avelumab at a given dose level of M9241, a safety review was performed by the Safety monitoring committee in order to make a decision on the next dose level. Successive cohorts of 3 to 6 subjects were treated with escalating doses of M9241 with avelumab intravenous (IV).

Publications & conference data

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

PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome.
Alsaab HO, Sau S, Alzhrani R, Tatiparti K, et al · · 2017 · cited 1206× · PMID 28878676 · DOI 10.3389/fphar.2017.00561
Localized Interleukin-12 for Cancer Immunotherapy.
Nguyen KG, Vrabel MR, Mantooth SM, Hopkins JJ, et al · · 2020 · cited 318× · PMID 33178203 · DOI 10.3389/fimmu.2020.575597
Targeting cytokine and chemokine signaling pathways for cancer therapy.
Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors.
Nayyar G, Chu Y, Cairo MS. · · 2019 · cited 135× · PMID 30805309 · DOI 10.3389/fonc.2019.00051
Biomarkers for immunotherapy in bladder cancer: a moving target.
Aggen DH, Drake CG. · · 2017 · cited 133× · PMID 29157296 · DOI 10.1186/s40425-017-0299-1
First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors.
Strauss J, Heery CR, Kim JW, Jochems C, et al · · 2019 · cited 130× · PMID 30131389 · DOI 10.1158/1078-0432.ccr-18-1512
Avelumab, an IgG1 anti-PD-L1 Immune Checkpoint Inhibitor, Triggers NK Cell-Mediated Cytotoxicity and Cytokine Production Against Triple Negative Breast Cancer Cells.
Juliá EP, Amante A, Pampena MB, Mordoh J, et al · · 2018 · cited 104× · PMID 30294328 · DOI 10.3389/fimmu.2018.02140
Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy.
Wang Y, Johnson KCC, Gatti-Mays ME, Li Z. · · 2022 · cited 103× · PMID 36031601 · DOI 10.1186/s13045-022-01335-y

Verify or expand the search:

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Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02994953 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by EMD Serono Research & Development Institute, Inc.
Last refreshed: 20 September 2024

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02994953.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing

NCT02994953: COMBO

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Serious adverse events (41 terms)

Sponsor's own description

Publications & conference data

Related trials

Other trials of Avelumab

Other recruiting trials for Advanced Solid Tumors

Other EMD Serono Research & Development Institute, Inc. trials

Verify against primary sources