Thoracic

Cohort A only: Have documented disease progression or be refractory to an anti-PD-1/PD-L1 antibody and a platinum-based chemotherapy regimen approved for NSCLC, either in combination or sequentially.

Cohort B only: Have not received prior systemic treatment for locally advanced or metastatic NSCLC and have PD-L1 ≥ 50% by local testing using an FDA-approved assay or in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory. Note: Prior adjuvant and neoadjuvant therapy are allowed prior to the development of metastatic disease, but adjuvant treatment must have been completed at least 6 months prior to Cycle 1 Day 1 (C1D1) and neoadjuvant treatment must have been completed at least 3 months prior to C1D1. Participants must have recovered from any prior AEs to Grade 1 or lower. 3.

Cohort A only: Last dose of previous anticancer therapy (including investigational agents) ≥ 28 days, radiotherapy ≥ 14 days (targeted palliative radiotherapy is allowed for lesions not planned for injections), or surgical intervention ≥ 21 days prior to C1D1

Cohort A only: Thyroid-stimulating hormone (TSH) within normal limits. If TSH is not within normal limits at baseline, total T3 or free T3 and free T4 must be within normal limits.

Inclusion:
Have systemic treatment naïve, histologically or cytologically confirmed diagnosis of Stage IIIB or IIIC (who are not amenable to curative surgery or radiotherapy) or Stage IV NSCLC
• Participants with non-squamous NSCLC will be enrolled to Substudy A. − Participants must be tested for EGFR mutations and ALK rearrangements; those with actionable results should not be enrolled. − If locally approved targeted first-line therapies are available, participants with known actionable mutations (other than EGFR and ALK alterations) should not be enrolled. Note: Testing for other genomic mutations is not mandated if not done as part of standard local practice.
• Participants with squamous NSCLC will be enrolled to Substudy B. Mixed tumors which involve squamous tumor cells will be categorized as squamous cell NSCLC; if small cell elements are present, the participant is ineligible. − If the participant is 15 years ago then they should be tested for EGFR mutations and ALK rearrangements; those with actionable results should not be enrolled

Exclusion:

Have received any of the following therapies or drugs within the noted time intervals prior to trial treatment:
• Previous chemotherapy (platinum-based) or PD(L)-1 for treating NSCLC in either neoadjuvant/adjuvant or locally advanced/metastatic setting.
• Receipt of an investigational drug or device within 30 days of screening or within five half-lives of the investigational drug (whichever is shorter).
• Participants who received prior treatment with anti-VEGF monoclonal antibody, or PD(L)-1/VEGF bispecific antibody.
• Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of trial treatment. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) are allowed.
• Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of the trial treatment.
• Received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of trial treatment.

Key Eligibility:

1. ECOG 0-2
2. No prior systemic therapy for advanced/metastatic NSCLC (prior adjuvant chemotherapy following
complete resection of early-stage NSCLC I-II is allowed)
3. Participants with 5 or fewer brain metastases are eligible if intracranial sites can be treated with
surgery and/or stereotactic radiosurgery, prior to initiation of chemo-immunotherapy
4. Visits: SOC Chemoimmunotherapy plus radiation to oligometastatic sites (frequency of radiation
visits determined on case by case basis)

Inclusion:
Have systemic treatment naïve, histologically or cytologically confirmed diagnosis of Stage IIIB or IIIC (who are not amenable to curative surgery or radiotherapy) or Stage IV NSCLC
• Participants with non-squamous NSCLC will be enrolled to Substudy A. − Participants must be tested for EGFR mutations and ALK rearrangements; those with actionable results should not be enrolled. − If locally approved targeted first-line therapies are available, participants with known actionable mutations (other than EGFR and ALK alterations) should not be enrolled. Note: Testing for other genomic mutations is not mandated if not done as part of standard local practice.
• Participants with squamous NSCLC will be enrolled to Substudy B. Mixed tumors which involve squamous tumor cells will be categorized as squamous cell NSCLC; if small cell elements are present, the participant is ineligible. − If the participant is 15 years ago then they should be tested for EGFR mutations and ALK rearrangements; those with actionable results should not be enrolled

Exclusion:

Have received any of the following therapies or drugs within the noted time intervals prior to trial treatment:
• Previous chemotherapy (platinum-based) or PD(L)-1 for treating NSCLC in either neoadjuvant/adjuvant or locally advanced/metastatic setting.
• Receipt of an investigational drug or device within 30 days of screening or within five half-lives of the investigational drug (whichever is shorter).
• Participants who received prior treatment with anti-VEGF monoclonal antibody, or PD(L)-1/VEGF bispecific antibody.
• Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of trial treatment. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) are allowed.
• Have been vaccinated with live attenuated vaccine(s) within 4 weeks prior to initiation of the trial treatment.
• Received broad-spectrum intravenous antibiotics therapy within 2 weeks prior to initiation of trial treatment.

Key Eligibility Criteria
Inclusion
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
• Expected life expectancy ≥ 3 months
• Metastatic (Stage IV) NSCLC
• Histologically or cytologically confirmed squamous or non-squamous NSCLC
• Tumor demonstrates high PD-L1 expression based on an IHC pharmDx 22C3 (TPS ≥50%) or SP263 (TC ≥50%) IHC clinical assay approved/cleared by local health authorities and in a laboratory compliant with national provisions; this can be obtained from available results, or from archival or fresh tumor tissue for measurement of PD-L1 expression at a local or central laboratory.
• At least one measurable noncerebral lesion according to RECIST v1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions since radiotherapy.
• No prior systemic treatment for metastatic NSCLC. Patients receiving adjuvant or neoadjuvant chemotherapy or curative-intent chemoradiotherapy and/or PD-1/L1 inhibitors are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease

Exclusion
• Histologic or cytopathologic evidence of the presence of small cell lung carcinoma.
• Known actionable genomic alterations (EGFR, ALK, ROS1, and BRAF V600E) for which first-line approved therapies are indicated. For patients with non-squamous histology, actionable driver mutation testing results are required before randomization.
• Has received any prior therapy for NSCLC in the metastatic setting
• Radiologically documented evidence of major blood vessel invasion (central pulmonary artery, central pulmonary veins, aorta, brachiocephalic artery, common carotid artery, subclavian artery, superior vena cava) or tumor invading organs (heart, trachea, esophagus, central bronchi [not including segmental bronchi]) or if there is a risk of esophagotracheal or esophagopleural fistula in the opinion of the investigator. b. Radiographic evidence of major blood vessel encasement with narrowing of the vessel or intratumor lung cavitation or necrosis that the investigator determines will pose a significantly increased risk of bleeding
• Symptomatic CNS metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease

Eligibility Criteria
Inclusion Criteria:
1. Single agent BCA101 - patients with the following tumor type will be eligible:
a. No prior history of treatment with anti-EGFR antibodies in the unresectable/metastatic setting (prior treatment with radiotherapy in the adjuvant setting is allowed).
2. Combination BCA101 and pembrolizumab - patients with the following tumor types will be eligible:
a. Patients must have no prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease) or prior history of immune checkpoint inhibitors with the exception of neoadjuvant therapy (>6 months prior to study drug initiation). No prior history of anti-EGFR antibodies (with the exception of radiosensitizing agents and multimodal treatment for locally advanced disease).
b. Patients must provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable.
c. Patients must have results from testing of human papillomavirus (HPV) status for oropharyngeal cancer
d. Patients must have progressed on one prior systemic therapy in the metastatic setting.
e. No prior history of treatment with anti-EGFR antibodies in the metastatic setting.
f. Expansion Cohort 6: Head and Neck Squamous Cell Carcinoma (HNSCC), metastatic or unresectable, recurrent with a Combined Positive Score (CPS) less than 1, as determined by PD-L1 IHC 22C3 pharmDx.
3. Randomized to either ficerafusp alfa alone or in combination with pembrolizumab -Expansion Cohort 9: Colorectal cancer (CRC) i. Patients must have received at least 2 and no more than 3 prior lines of systemic therapy including two standard treatment regimens.

Exclusion Criteria:
1. Prior treatment with any anti-TGFb therapy.
2. Has a history of (non-infectious) pneumonitis, radiation pneumonitis or interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.

For pre-screening, please contact: Message Basket: VICC RESEARCH PHASE 1

Key Eligibility Criteria:

Inclusion:
1. < 40 years of age at the time of enrollment
2. Patient must be a post-menarchal female and report that their initial menstrual period occurred > 6 months prior to enrollment. (Current menstrual status is not part of the inclusion criteria.)
3. Newly diagnosed with first cancer, exclusive of breast cancer.
4. Planned treatment must include one or more of the following alkylating agents delivered with curative intent: cyclophosphamide, ifosfamide, procarbazine, chlorambucil, carmustine (BCNU), lomustine (CCNU), melphalan, thiotepa, busulfan, nitrogen mustard.
5. For patients < 20 years of age at enrollment, the expected alkylator dose must be ≥ 4 g/m^2 cumulative cyclophosphamide equivalent dose (CED). For patients ≥ 20 years of age at enrollment, any planned alkylator dose is permitted. Eligible patients must receive at least one of the alkylators that contribute to CED.

Exclusion:
1. Any planned radiation to the pelvis; or cranial radiation ≥ 30 gray (Gy) to the hypothalamus, inclusive of any total body irradiation (TBI).
2. Planned bilateral oophorectomy. Note: A participant's desire to pursue alternative fertility preservation procedures (i.e., embryo, oocyte, or ovarian tissue cryopreservation) will be allowed (and in fact encouraged).
3. Receipt of long acting (depot) GnRH agonists within 6 months before enrollment. In contrast, subcutaneous GnRH agonist used for oocyte retrieval is not an exclusion; oral and other hormonal contraceptive use is also not an exclusion. Note: Please see protocol for the concomitant therapy restrictions for patients during the study treatment period. See protocol for information about oral and other hormonal contractive use during the study treatment period.
4. Prior receipt of systemic chemotherapy. However, steroids and intrathecal chemotherapy are permitted prior to study enrollment.
5. Any prior radiation to the pelvis; or cranial radiation ≥ 30 Gy to the hypothalamus, inclusive of any total body irradiation (TBI).

For pre-screening, please contact: Please reach out to the Disease specific research teams.

Key Eligibility Criteria:

Inclusion Criteria:
1. Planned intravenous treatment with a minimum of 12 weeks of neurotoxic chemotherapy treatment and with no planned treatment pause for surgery during neurotoxic chemotherapy treatment.
a. With one of the following treatments:
i. Chemotherapy regimens based on Oxaliplatin
1. FOLFOX every 2 weeks
2. FOLFIRINOX every 2 weeks
ii. Chemotherapy regimens based on single-agent Paclitaxel
1. Paclitaxel weekly
2. Paclitaxel every 3 weeks
iii. Chemotherapy regimens based on Paclitaxel + Carboplatin
1. Paclitaxel weekly with Carboplatin weekly/every 3 weeks
2. Paclitaxel every 3 weeks with Carboplatin every 3 weeks
b. Concurrent administration of the chemotherapies listed in the inclusion criteria with or without targeted agents/immunotherapy at standard doses is allowed (such as trastuzumab, pertuzumab, bevacizumab, pembrolizumab or other immune checkpoint inhibitors).
2. Planned taxane or platinum containing portion of chemotherapy regimen prescribed to last at least 12 weeks in duration and less than or equal to 12 months in duration. Note: The regimen is prescribed as per physician discretion in accordance with standard of care guidelines.

Exclusion Criteria:
1. Baseline peripheral neuropathy of any kind as defined by NCI CTCAE v5.0 grade > 0.
2. Any open wounds, sores, cysts or injury on the participant's hand or on part of the upper arm where the device will be applied or on the participant's feet or part of the lower leg where the device will be applied, which in the opinion of the investigator will not be healed prior to infusion commencing or who in the opinion of the investigator will be inappropriate for inclusion in this study.
3. Weight greater than 140 kg at the time of enrollment.
4. Participants who are receiving neuropathy directed systemic therapies at the time of enrollment, namely, Pregabalin, Gabapentin, Amitriptyline, Nortriptyline, Venlafaxine, Duloxetine.

For pre-screening, please contact: Reach out to the disease specific research team.