Trial Outcomes & Findings for Phase Ib/II Study of Carboplatin + M6620 + Avelumab in PARPi-resistant Ovarian Cancer (NCT NCT03704467)

Last Updated: 2020-11-13

Results Overview

DLT: any death not clearly due to underlying disease/extraneous causes/Grade(Gr) \>=3 nonhematologic/Gr\>=4 hematologic toxicity that was probably/definitely related to any of study interventions, individually/combination that occurred during DLT observation period, except for any of following: Gr3 infusion-related reaction; Transient (\<=6hr) Gr3 flu-like symptoms/fever, controlled with medical management; Transient (\<=72hr) Gr3 fatigue, local reactions, headache, nausea/emesis; Gr3 diarrhea, skin toxicity, liver function test increase; Single laboratory values out of normal range and controlled with medical management; Tumor flare phenomenon: local pain, irritation/rash, localized at sites of known/suspected tumor; Neutropenia (Gr3/4) for \<7 days not associated with any infection; Gr3 thrombocytopenia for \<7 days without clinically significant bleeding and not requiring platelet transfusion; Symptomatic thyroid dysfunction manageable with treatment.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

3 participants

Primary outcome timeframe

Up to 3 weeks

Results posted on

2020-11-13

Participant Flow

First participant signed informed consent: 04 Mar 2019, Last participant last visit: 06 Nov 2019.

This study was planned to be conducted in 2 parts; Part A was the safety run-in part and Part 2 was the randomized controlled part. However, after completing Part A and confirming the safe combination dose, the sponsor decided not to conduct Part B.

Participant milestones

Participant milestones
Measure	Part A: Carboplatin + M6620 + Avelumab Participants received intravenous infusion of Carboplatin area under the concentration-time curve 5 on Day 1 in combination with 90 milligrams per square meter (mg/m\^2) of M6620 on Day 2 and avelumab at an established dose of 1600 mg over 60 minutes on Day 1 for every 3 weeks cycle for a maximum of 6 cycles. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase Ib/II Study of Carboplatin + M6620 + Avelumab in PARPi-resistant Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Carboplatin + M6620 + Avelumab n=3 Participants Participants received intravenous infusion of Carboplatin area under the concentration-time curve 5 on Day 1 in combination with 90 milligrams per square meter (mg/m\^2) of M6620 on Day 2 and avelumab at an established dose of 1600 mg over 60 minutes on Day 1 for every 3 weeks cycle for a maximum of 6 cycles. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 weeks

Population: DLT analysis set included all evaluable participants with data used for implementing the dose-escalation schedule. These participants received at least 1 study intervention administration of each avelumab, M6620, and/or chemotherapy in the DLT evaluation period or should have stopped treatment because of DLTs in the DLT evaluation period.

Outcome measures

Outcome measures
Measure	Part A: Carboplatin + M6620 + Avelumab n=3 Participants Participants received intravenous infusion of Carboplatin area under the concentration-time curve 5 on Day 1 in combination with 90 milligrams per square meter (mg/m\^2) of M6620 on Day 2 and avelumab at an established dose of 1600 mg over 60 minutes on Day 1 for every 3 weeks cycle for a maximum of 6 cycles. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Part A: Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants

SECONDARY outcome

Timeframe: Time from first dose of study treatment up to 230 days

Population: Safety analysis set included all participants who received at least 1 dose of any study intervention.

An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was 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. TEAEs were defined as events that started or worsened after first dose of study intervention until 30 days after last dose. TEAEs included both serious and non-serious AEs. Treatment-related TEAE: reasonably related to the study intervention. The AE could medically (pharmacologically/clinically) be attributed to the study intervention under study in this clinical study protocol.

Outcome measures

Outcome measures
Measure	Part A: Carboplatin + M6620 + Avelumab n=3 Participants Participants received intravenous infusion of Carboplatin area under the concentration-time curve 5 on Day 1 in combination with 90 milligrams per square meter (mg/m\^2) of M6620 on Day 2 and avelumab at an established dose of 1600 mg over 60 minutes on Day 1 for every 3 weeks cycle for a maximum of 6 cycles. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs TEAEs	3 Participants
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs Treatment-Related TEAEs	3 Participants

SECONDARY outcome

Timeframe: Time from first dose of study treatment up to 230 days

Population: Safety analysis set included all participants who received at least 1 dose of any study intervention.

Confirmed BOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression/ 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% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with BOR in each category (CR, PR, SD, PD) were reported.

Outcome measures

Outcome measures
Measure	Part A: Carboplatin + M6620 + Avelumab n=3 Participants Participants received intravenous infusion of Carboplatin area under the concentration-time curve 5 on Day 1 in combination with 90 milligrams per square meter (mg/m\^2) of M6620 on Day 2 and avelumab at an established dose of 1600 mg over 60 minutes on Day 1 for every 3 weeks cycle for a maximum of 6 cycles. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Part A: Number of Participants With Confirmed Best Overall Response (BOR) Complete Response	0 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) Partial Response	0 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) Stable Disease	1 Participants
Part A: Number of Participants With Confirmed Best Overall Response (BOR) Progressive Disease	2 Participants

SECONDARY outcome

Timeframe: Time from first dose of study treatment up to 230 days

Population: Safety analysis set was used. No summary analysis was done as study was early discontinued as per Sponsor's decision and participant wise data was reported. Here, "Number Analyzed" signifies specific participant evaluated in the arm of this outcome measure.

PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from date of randomization until date of the first observation of progressive disease (PD) or death due to any cause within 12 weeks of the last tumor assessment in the absence of documented PD, whichever occurs first. PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Participant wise data reported for this outcome measure.

Outcome measures

Outcome measures
Measure	Part A: Carboplatin + M6620 + Avelumab n=3 Participants Participants received intravenous infusion of Carboplatin area under the concentration-time curve 5 on Day 1 in combination with 90 milligrams per square meter (mg/m\^2) of M6620 on Day 2 and avelumab at an established dose of 1600 mg over 60 minutes on Day 1 for every 3 weeks cycle for a maximum of 6 cycles. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Part A: Progression-Free Survival (PFS) Participant 2	2.1 months
Part A: Progression-Free Survival (PFS) Participant 3	6.1 months
Part A: Progression-Free Survival (PFS) Participant 1	1.9 months

SECONDARY outcome

Timeframe: Time from first dose of study treatment up to 230 days

Population: Data could not be calculated as none of the participants showed objective response.

DoR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of objective progression of disease (PD) or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. If a participant has not an event (PD or death), DoR was censored at the date of last adequate tumor assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from first dose of study treatment up to 230 days

Population: Safety analysis set was used. No summary analysis was done as study was early discontinued as per Sponsor's decision and participant wise data was reported. Here, "Overall Number of Participants Analyzed" = participants who were evaluable for this outcome measure and "number analyzed" = specific participants evaluated in the arm.

TTP according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and assessed by an Investigator was defined as the time from first dose of study intervention until progression disease (PD). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Participant wise data reported for this outcome measure.

Outcome measures

Outcome measures
Measure	Part A: Carboplatin + M6620 + Avelumab n=2 Participants Participants received intravenous infusion of Carboplatin area under the concentration-time curve 5 on Day 1 in combination with 90 milligrams per square meter (mg/m\^2) of M6620 on Day 2 and avelumab at an established dose of 1600 mg over 60 minutes on Day 1 for every 3 weeks cycle for a maximum of 6 cycles. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Part A: Time to Progression (TTP) Participant 1	1.9 months
Part A: Time to Progression (TTP) Participant 2	2.1 months

SECONDARY outcome

Timeframe: From date of randomization to the earliest date of first subsequent therapy or death, assessed up to 230 days

Population: Data could not be calculated since the date of first subsequent treatment was not recorded in the electronic case report form (eCRF) as per changes in planned analysis.

The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death.