| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced/metastatic solid tumors |
|
| E.1.1.1 | Medical condition in easily understood language |
| People with advance solid tumor cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065252 |
| E.1.2 | Term | Solid tumor |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. To evaluate the objective response rate (ORR) of V937 administered in subcutaneous tumors in combination with pembrolizumab per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the investigator.
2. To determine the safety and tolerability and to establish a preliminary recommended phase 2 dose (RP2D) of V937 administered in visceral tumors in combination with pembrolizumab. |
|
| E.2.2 | Secondary objectives of the trial |
1. To determine the safety and tolerability of V937 administered in subcutaneous tumors in combination with pembrolizumab.
2. To evaluate progression free survival (PFS), and duration of response (DOR) of participants treated with V937 in subcutaneous tumors in combination with pembrolizumab per RECIST 1.1 as assessed by the investigator.
3. To evaluate the ORR, PFS and DOR of V937 administered in subcutaneous tumors in combination with pembrolizumab per RECIST 1.1 for immune-based therapeutics (iRECIST) criteria as assessed by the investigator.
4. To evaluate overall survival (OS) of participants treated with V937 in subcutaneous tumors in combination with pembrolizumab.
5. To evaluate the ORR of V937 administered in visceral tumors at the preliminary RP2D with pembrolizumab per RECIST 1.1 and iRECIST criteria as assessed by the investigator. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Has locally-advanced disease that is not amenable to surgery or radiation, or Stage IV advanced/metastatic solid tumor malignancies
2. Has histologically- or cytologically-confirmed diagnosis of an advanced/metastatic solid tumor
3. Has measurable disease by RECIST 1.1 criteria as assessed by investigator. Target lesions in a previously irradiated area will be considered measurable if progression has been demonstrated in such lesions
4. Has submitted a baseline tumor sample for analysis (either de novo biopsy or an archival tumor block)
5. Has a performance status of 0 or 1 on the ECOG Performance Scale obtained within 72 hours prior to the first dose of study intervention
6. If participants have known HIV-positive disease, participants must have well-controlled HIV on ART defined as:
a. CD4+ T-cell count >350 cells/mm3 at the time of screening
b. Must have achieved and maintained virologic suppression, defined as HIV RNA levels below 50, or LLOQ (below limits of detection), using a locally available assay at the time of screening
c. Must be on a stable regimen without any changes in drugs or dose modifications for a minimum of 4 weeks prior to study entry (Day 1)
7. Demonstrate adequate organ function
8. Is male or female, from ≥18 years of age inclusive, at the time of signing the informed consent
9. Male participants are eligible to participate if they agree to the following during the intervention period for and for at least 120 days after the last dose of study intervention:
PLUS either:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
- Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below:
Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a WOCBP
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention
- A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 72 hours before the first dose of study intervention
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
-The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
11. The participant (or legally acceptable representative) provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research |
|
| E.4 | Principal exclusion criteria |
1. Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to first dose of study intervention, or has not recovered to CTCAE Grade 1 or better
2. If major or minor surgery was performed at/near the area being considered for injection, participant must be recovered from toxicity and/or complications of intervention
3. Has had injection, or radiation therapy of >30 Gy, participant must be recovered from toxicity and/or complications of intervention
4. Has a history of second malignancy, unless potentially curative treatment has been completed with no further evidence of malignancy
5. Has known active CNS metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if lesions are radiologically stable
6. Has an active infection requiring therapy
7. Has a history of interstitial lung disease
8. Has a history of noninfectious pneumonitis requiring active steroid therapy or ongoing pneumonitis
9. Has an active autoimmune disease that required systemic treatment in the past 2 years (ie, necessitating use of disease modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid replacement therapy (steroid use ≤10 mg prednisone, or its equivalent, daily) is not considered a form of systemic treatment and is allowed. The use of non-systemic steroids is permitted
10. Participants with known Hepatitis B or C infections or known to be positive for HBsAg/HBV DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay
11. Participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
12. Has known hypersensitivity to V937 and/or pembrolizumab or any of their excipients
13.Has known psychiatric or substance abuse disorder that significantly interferes with cooperation with requirements of the trial
14. Has received prior therapy with anti-PD-1/PD-L1 agents, T-VEC or any other oncolytic virus therapies
15. Has received a live or live-attenuated vaccine within 30 days prior to first dose of study intervention.
16. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
17. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Part 1: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
2. Number of Participants who Experience a Dose-Limiting Toxicity (DLT)
3. Part 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
4. Part 2: Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 5 years.
2. Up to approximately 4 weeks
3. Up to approximately 107 weeks
4. Up to approximately 103 weeks
|
|
| E.5.2 | Secondary end point(s) |
1. Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs)
2. Part 1: Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
3. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
4. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
5. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
6. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
7. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator
8. Overall Survival (OS)
9. Solid Tumors+Liver Metastases Arms: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 107 weeks.
2. Up to approximately 103 weeks.
3. Up to approximately 5 years.
4. Up to approximately 5 years.
5. Up to approximately 5 years.
6. Up to approximately 5 years.
7. Up to approximately 5 years.
8. Up to approximately 5 years.
9. Up to approximately 5 years
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 13 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Brazil |
| Canada |
| Israel |
| Peru |
| Taiwan |
| United States |
| France |
| Germany |
| Hungary |
| Italy |
| Norway |
| Poland |
| Portugal |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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