A Phase 1b/2 Study to Evaluate Safety and Clinical Activity of Avelumab in Combination with Bempegaldesleukin with or without Talazoparib or Enzalutamide in Participants with Locally Advanced or Metastatic Solid Tumors

Phase 1

Conditions: ocally recurrent (not amenable for curative intent) or metastatic squamous cell carcinoma of the of the oral cavity, oropharynx, hypopharynx, or larynx
metastatic castration-resistant prostate cancer without small cell features
MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10063569Term: Metastatic squamous cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-001358-24-BE

Lead Sponsor: Pfizer Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 127

Inclusion Criteria

SCCHN and mCRPC
- >/= 18 years of age and give consent
- Must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures as specified in the protocol
- Contraceptive use must meet requirements outlined in the protocol and should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- COG of 0 or 1
- Participants must have adequate bone marrow function without hematopoietic growth factor or transfusion support within 14 days prior to and including C1D1 per protocol
- Participants must have adequate liver function by C1D1 per protocol
- Participants must have adequate renal function by C1D1 per protocol
- All participants must provide tumor tissue as described in protocol
Combination A- SCCHN
- Histological diagnosis of locally recurrent (not amenable for curative intent) or metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx and both of the following:
- No prior systemic treatment for unresectable locally recurrent or metastatic disease
Exception: If prior systemic chemotherapy treatment was given as part of chemoradiotherapy treatment, disease-free interval after the last administration of systemic chemotherapy treatment must be at least 6 months
- Measurable disease by RECIST v1.1 with at least 1 measurable lesion
Combination B & C- mCRPC
- mCRPC without small cell features meeting the following criteria:
- Castration as defined by both of the following:
- Serum testosterone =1.73 nmol/L (50 ng/dL) at the time of enrollment (prior to treatment with study drug on C1D1)
- Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist (surgical or medical castration)
- Progressive disease at the time of enrollment (prior to treatment with study drug on C1D1) defined as 1 or more of the following 3 criteria:
- A minimum of 3 consecutive rising PSA values with an interval of at least 1 week between determinations.
- The screening PSA value must be =2 µg/L (2 ng/mL) if qualifying solely by PSA progression
- Radiographic soft tissue disease progression as defined by RECIST v1.1 for soft tissue
- Radiographic bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or more new metastatic lesions on bone scan (confirm ambiguous results by other imaging modalities)
Combination B only (mCRPC)
- Progressed on at least 1 line of second generation anti-androgen therapy (e.g. enzalutamide and/or abiraterone acetate/prednisone) for treatment of mCRPC
- Have received at least 1, but no more than 1, prior taxane-based chemotherapy regimens for mCRPC or were deemed unsuitable, declined, or did not have access to these therapies
- Participants may have received radium -223, which does not count for a line of prior chemotherapy regimen
- Measurable disease by RECIST v1.1 with at least 1 measurable lesion
Phase 2 Only:
- Required to have their disease assessed for a genomic defect in one or more pre-defined DDR genes based on testing de novo or archival tumor tissue using the Foundation One® Test
Combination C only (mCRPC)
- Participants with non-measurable disease (including disease affecting bone only) as determined by RECIST v1.1 are allowed
- Participants must have progressed on 1 line of abiraterone acetate/prednisone anti-androgen therapy for treatment of mCRPC
- Participants

Exclusion Criteria

SCCHN and mCRPC
- Known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCT CTCAE v4.03 Grade =3)
- Known history of: immune-mediated colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis
- Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
- Participants with diabetes type I, vitiligo, psoriasis, or hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible
- Prior organ transplantation
- Vaccination within 4 weeks prior to C1D1 and while on trial is prohibited except for administration of inactivated vaccines
- Known symptomatic brain lesions requiring steroids
Exception: participants with previously diagnosed brain lesions are eligible if they meet all of the following criteria:
have newly diagnosed small brain lesions which do not require treatment
have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to C1D1
have discontinued corticosteroid treatment for these lesions for at least 4 weeks prior to C1D1; and are neurologically stable
Known history of testing positive for HIV or known AIDS
- Positive HBV surface antigen, or positive HCV RNA if anti-HCV antibody screening tests positive
- Active infection requiring systemic therapy within 14 days prior to C1D1.
- Other acute or chronic medical or psychiatric conditions
- Clinically significant (i.e., active) cardiovascular disease including the following:
- Documented left ventricular ejection fraction < 45%
- Cerebral vascular accident/stroke, Myocardial infarction (<6 months prior to C1D1)
- Unstable angina
- Congestive heart failure
- Serious cardiac arrhythmia requiring medication
- Diagnosis of any other malignancy within 2 years prior to C1D1, except for adequately treated basal cell or quamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix
- Prior immunotherapy with IL-2 agents or anti PD-1, anti PD-L1, anti PD-L2, or anti- CTLA-4 antibody. Prior treatment with Sipuleucel-T for participants with mCRPC is allowed
- Current use of immunosuppressive medication at the time of C1D1, EXCEPT for the following permitted steroids:
- Intranasal, inhaled, topical steroids, eye drops or local steroid injection; systemic corticosteroids at physiologic doses =10 mg/day of prednisone; steroids as premedication for hypersensitivity reactions
- Bisphosphonate or denosumab dosage that was not stable for at least 2 weeks before C1D1 for participants receiving these therapies
- Prior radiation therapy within 14 days prior to C1D1. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed > 14 days prior to C1D1 and no clinically significant toxicities are expected
- Major surgery within 4 weeks prior to C1D1
- Participation in other studies involving investigational drug(s) within 2 weeks prior to C1D1
- Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade >1); however, alopecia and sensory neuropathy Grade =2, or other Grade =2 AEs not constituting a safety risk, based on Investigator's judgment (I’s), are acceptable
- I site staff members or participants who are Pfizer employees, directly involved in the conduct of the study and their family, site staff members otherwise supervised by th

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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