Safety and Efficacy Study of Vociprotafib (SAR442720) in Combination With Other Agents in Advanced Malignancies

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• Neoplasm Metastasis 3,517

Neoplasm Metastasis

3,517 studies on the registry are indexed under Neoplasm Metastasis; 885 are open to participants now.

This study's enrollment of 65 is above the median of 54 across 2,767 interventional studies indexed under Neoplasm Metastasis.

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Study arms

• Experimental
  Part 1- SAR442720 140 mg BIW + Pembrolizumab

  Participants were administered SAR442720 140 milligram (mg) orally twice a week (BIW) on Days 1 and 4 along with pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) in 21-day cycles until disease progression, unacceptable adverse events (AEs), or the participant's or investigator's decision to stop the treatment.

  Drug: Vociprotafib · Drug: Pembrolizumab

• Experimental
  Part 1- SAR442720 200mg BIW + Pembrolizumab

  Participants were administered SAR442720 200 mg orally BIW on Days 1 and 2 along with pembrolizumab 200 mg via IV infusion Q3W in 21-day cycles until disease progression, unacceptable AEs, or the participant's or investigator's decision to stop the treatment.

  Drug: Vociprotafib · Drug: Pembrolizumab

• Experimental
  Part 2- SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%)

  Participants with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS)\>=50% non-small cell lung cancer (NSCLC) were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles along with an IV infusion of pembrolizumab 200 mg on Q3W (21 days cycle) or 400 mg once in every 6 weeks (Q6W) (42 days cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.

  Drug: Vociprotafib · Drug: Pembrolizumab

• Experimental
  Part 2- SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%)

  Participants with PDL1 TPS 1% - 49% NSCLC were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles along with an IV infusion of pembrolizumab 200 mg on Q3W (21 days cycle) or 400 mg Q6W (42 days cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.

  Drug: Vociprotafib · Drug: Pembrolizumab

• Experimental
  Part 3A- SAR442720 100mg BIW + Adagrasib

  Participants were administered SAR442720 100 mg orally BIW on Days 1 and 2 along with adagrasib 400 mg orally twice daily (BID) in 21-day cycles until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.

  Drug: Vociprotafib · Drug: Adagrasib

• Experimental
  Part 4- SAR442720 200mg + Pembrolizumab

  Participants were administered SAR442720 200 mg orally BIW on Days 1 and 2 in 21-day cycles (as tablet during the first cycle and as capsule from Cycle 2) along with an IV infusion of pembrolizumab 200 mg Q3W (21-day cycle)or 400 mg Q6W (42-day cycle) until disease progression, unacceptable AEs, consent withdrawal, or the participant's or investigator's decision to stop the treatment.

  Drug: Vociprotafib · Drug: Pembrolizumab

Interventions

• DrugVociprotafib

  Pharmaceutical form: Varies Route of administration: Varies

  Also known as: SAR442720, RMC-4630

• DrugPembrolizumab

  Pharmaceutical form:Sterile Lyophilized powder for reconstitution Route of administration: Infusion

• DrugAdagrasib

  Pharmaceutical form:Sterile Tablet Route of administration: Oral

Primary outcomes

1. Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

   AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.

   Time frame: From first dose of IMP up to 30 days after the last dose; approximately 27 weeks

2. Parts 1 and 3A: Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs)

   Potential DLTs were defined as the AEs that occurred during the first cycle (C) of treatment, considered by the investigator to be related to IMP, unless due to disease progression or to a cause obviously unrelated to IMP: Grade(G)\>= 4 AEs, G3 neutropenia lasting \>7 days or febrile neutropenia; G3 thrombocytopenia with clinically significant bleeding; any G\>=3 immune-related AEs; G3 nonhematologic AEs; G3 aspartate transaminase, alanine transaminase, and/or total bilirubin elevations that persist \>5 days; possible Hy's law case; G3 QT interval corrected using Fridericia's formula prolongation; retinal vein occlusion any grade; toxicity related to IMP leading to 50% or less dose intensity of SAR442720 and/or delay in initiation of C2 dosing of pembrolizumab by \>15 days, in the absence of recovery to baseline or G \<=1 AE. Potential DLT were reviewed by Sponsor and investigators to confirm them as DLTs.

   Time frame: Cycle 1 (21 days)

3. Part 2: Percentage of Participants With Objective Response Rate (ORR)

   ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) determined by investigator per response evaluation criteria in solid tumors (RECIST) version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 millimeter (mm) OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The confidence interval (CI) was estimated using Clopper-Pearson method.

   Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks

4. Part 3A: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events

   AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.

   Time frame: From first dose of IMP up to 30 days after the last dose; approximately 7 weeks

5. Part 4: Plasma Concentration of SAR442720 in Combination With Pembrolizumab

   Plasma samples were collected at specified timepoints for pharmacokinetic (PK) analysis.

   Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on C1 D1, C1 D15, C2 D1; Pre-dose on C1 D8 and C6 D1; end of treatment (Week 45)

6. Part 4: Area Under Curve From Zero to Last Concentration Timepoint (AUClast) for SAR442720 Tablets and Capsules

   Plasma samples were collected at specified timepoints to determine AUClast for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using non-compartmental analysis (NCA) method.

   Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2D1

7. Part 4: Maximum Observed Plasma Concentration (Cmax) for SAR442720 Tablets and Capsules

   Plasma samples were collected at specified timepoints to determine Cmax for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using NCA method.

   Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1

8. Part 4: Time to Reach Maximum Plasma Concentration (Tmax) for SAR442720 Tablets and Capsules

   Plasma samples were collected at specified timepoints to determine tmax for evaluating the impact of food and formulation on the PK of SAR442720 tablet. It was calculated using NCA method.

   Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours on C1 D1, C1 D15 and C2 D1

Secondary outcomes

1. Part 1: Plasma Concentration of SAR442720

   Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations.

   Time frame: Pre-dose, 2, 8, hours post-dose on C1 D1 and C2D1; pre-dose C1D8, C1D15, and C6D1; 2 hours C2D2; and end of treatment (Week 22)

2. Part 2: Plasma Concentration of SAR442720

   Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations.

   Time frame: Pre-dose and 2 hours post-dose C1D1 and C2D1; pre-dose on C1D8, C1D15, C6D1; and end of treatment (Week 104)

3. Parts 1 and 2: Serum Concentration of Pembrolizumab

   Serum samples were collected at specified timepoints for evaluation of pembrolizumab PK concentrations.

   Time frame: Pre-dose and post-dose C1D1; pre-dose on C2D1 and C6D1

4. Parts 1 and 4: Percentage of Participants With Objective Response Rate

   ORR was defined as the percentage of participants who had a confirmed CR or PR determined by investigator per RECIST version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The CI was estimated using Clopper-Pearson method.

   Time frame: Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks (Part 1), 46 weeks (Part 4)

5. Part 1: Duration of Response (DoR)

   DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive disease progression(PD) or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. DoR was estimated using Kaplan-Meier method.

   Time frame: Tumor assessments performed on C3 D1 (± 7 days) and every 2 cycles up to C7 D1 (± 7 days), and then every 3 cycles thereafter, approximately 23.7 weeks

6. Part 2: Duration of Response

   DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive PD or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5mm. DoR was estimated using Kaplan-Meier method.

   Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks

7. Part 2: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events

   AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.

   Time frame: From first dose of IMP up to 30 days after the last dose; approximately 111 weeks

8. Part 4: Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events

   AE: any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. TEAEs: AEs that developed or worsened or became serious during treatment-emergent period, defined as time from first administration of IMP (on Day 1) to last administration of IMP + 30 days. SAE: any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event.

   Time frame: From first dose of IMP up to 30 days after the last dose; approximately 50 weeks

9. Part 2: Time to Response (TTR)

   TTR was defined as the time interval from the administration of first IMP dose to the first documented evidence of PR or CR determined by the Investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. TTR was estimated using Kaplan-Meier method.

   Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks

10. Part 2: Percentage of Participants With Clinical Benefit Rate

    Clinical benefit rate was defined as the percentage of participants with confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The CI was estimated using Clopper-Pearson method.

    Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks

11. Part 2: Percentage of Participants With Disease Control Rate

    Disease control rate was defined percentage of participants with confirmed CR or PR or SD as determined by the investigator per RECIST version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The CI was estimated using Clopper-Pearson method.

    Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks

12. Part 2: Progression Free Survival (PFS)

    PFS was defined as the time from the date of first IMP administration to the date of the first documented PD determined by the investigator per RECIST version 1.1 or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. PFS was estimated using Kaplan-Meier method.

    Time frame: Tumor assessments performed every 9 weeks (56 ±7 days) after the date of first IMP up to end of treatment, approximately 107 weeks

13. Part 3A: Plasma Concentration of SAR442720

    Plasma samples were collected at specified timepoints for evaluation of SAR442720 PK concentrations. It was calculated using NCA method.

    Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 24 hours post-dose C1D1; pre-dose C1D8; pre-dose, 0.5, 1, 2, 4, 6 post-dose C1D15, and end of treatment (Week 3)

14. Part 3A: Plasma Concentration of Adagrasib

    Plasma samples were collected at specified timepoints for evaluation of adagrasib PK concentrations. It was calculated using NCA method.

    Time frame: Pre-dose, 1, 2, 4, 6, 8 post-dose C1D1 and C1D15; pre-dose C1D8

15. Part 3A: Percentage of Participants With Objective Response Rate

    ORR was defined as the percentage of participants who had a confirmed CR or PR determined by investigator per RECIST version 1.1 CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The CI was estimated using Clopper-Pearson method.

    Time frame: Tumor assessments performed till end of treatment, approximately 3 weeks

16. Part 3A: Duration of Response

    DoR as per RECIST version 1.1 was defined as the interval from the first documentation of CR or PR to the earlier of first documentation of definitive PD or death due to any cause, whichever occurs first. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) had reduction in short axis to 10 mm OR disappearance of all nontarget lesions and normalization of tumor marker level. All lymph nodes had nonpathological in size (\< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. DoR was estimated using Kaplan-Meier method.

    Time frame: Tumor assessments performed till end of treatment, approximately 3 weeks

Baseline characteristics

Related links

• TCD16210 Plain language Results Summary ↗

Study documents

• Study protocol · Oct 26, 2021
• Statistical analysis plan · Jul 14, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org